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  • 1.
    Ding, Zhen-Yu
    et al.
    Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Country Council of Östergötland, University of Linköping, Linköping, Sweden; Department of Thoracic Oncology, Cancer Center, and the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
    Zhang, Hong
    Örebro universitet, Institutionen för läkarutbildning.
    Adell, Gunnar
    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Olsson, Birgit
    Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Country Council of Östergötland, University of Linköping, Linköping, Sweden.
    Sun, Xiao-Feng
    Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Country Council of Östergötland, University of Linköping, Linköping, Sweden.
    Livin expression is an independent factor in rectal cancer patients with or without preoperative radiotherapy2013Ingår i: Radiation Oncology, ISSN 1748-717X, E-ISSN 1748-717X, Vol. 8, nr 1, artikel-id 281Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: This study was aimed to investigate the expression significance of Livin in relation to radiotherapy (RT), clinicopathological and biological factors of rectal cancer patients.

    Methods: This study included 144 primary rectal cancer patients who participated in a Swedish clinical trial of preoperative radiotherapy. Tissue microarray samples from the excised primary rectal cancers, normal mucosa and lymph node metastases were immunostained with Livin antibody. The proliferation of colon cancer cell lines SW620 and RKO was assayed after Livin knock-down.

    Results: The expression of Livin was significantly increased from adjacent (P = 0.051) or distant (P = 0.028) normal mucosa to primary tumors. 15.4% (2/13) and 39.7% (52/131) patients with Livin-negative and positive tumors died at 180 months after surgery, and the difference tended to be statistically significant (P = 0.091). In multivariate analyses, the difference achieved statistical significance, independent of TNM stage, local and distant recurrence, grade of differentiation, gender, and age (odds ratio = 5.09, 95% CI: 1.01-25.64, P = 0.048). The in vitro study indicated colon cancer cells with Livin knock-down exhibited decreased proliferation compared with controls after RT.

    Conclusions: The expression of Livin was was independently related to survival in rectal cancer patients, suggesting Livin as a useful prognostic factor for rectal cancer patients.

  • 2.
    Evert, Jasmine
    et al.
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Pathak, Surajit
    Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Faculty of Allied Health Sciences, Chettinad Academy of Research and Education, Kelambakkam, India.
    Sun, Xiao-Feng
    Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Zhang, Hong
    Örebro universitet, Institutionen för medicinska vetenskaper.
    A Study on Effect of Oxaliplatin in MicroRNA Expression in Human Colon Cancer2018Ingår i: Journal of Cancer, ISSN 1837-9664, E-ISSN 1837-9664, Vol. 9, nr 11, s. 2046-2053Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Colorectal cancer is a commonly diagnosed malignancy and also the major cause of death worldwide. Chemotherapy is the primary therapy for advanced colorectal cancer. Although oxaliplatin has potential effect in colorectal cancer therapy, the molecular mechanisms involved in its cytotoxic effects are not well elucidated. This study outlines the regulatory effects of oxaliplatin on miRNAs expression in colon cancer cells and correlates it with the changing microRNA expression with p53 and p73 expression status in cells. HCT116(p53+/+) and HCT116(p53-/-) cells were exposed to oxaliplatin, and the cellular viability was determined by XTT. p73 was knocked down using siRNA and the tumor cells were then treated with oxaliplatin. The expression profile of 384 miRNAs was determined by TaqMan (R) human miRNA array and calculated by the Delta Delta C-t method. Cellular viability was found to decrease after the treatment with oxaliplatin in a dose-dependent manner. The wild-type p53 cells were found to be more sensitive than the null-p53 derivatives. A selective set of miRNAs were either up-regulated or down-regulated in response to the oxaliplatin treatment with a presumable role of p53 and p73 proteins. The miRNAs expression is known to influence the pharmacodynamic mechanisms of oxaliplatin and these effects have been observed to be regulated by p53 and p73. Our results may therefore provide more evidence for identifying a suitable biomarker for the diagnosis of colon cancer.

  • 3.
    Evert, Jasmine
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Pathak, Surajit
    Linköping University.
    Sun, Xiao-Feng
    Linköping University.
    Zhang, Hong
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Modification of microRNA expression profiles by oxaliplatin, p53 and p73 in human colon cancer cells in vitroManuskript (preprint) (Övrigt vetenskapligt)
  • 4.
    Fan, Chuan-Wen
    et al.
    Institute of Digestive Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China; Department of Oncology, Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Kopsida, Maria
    Department of Oncology, Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Liu, You-Bin
    Institute of Digestive Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China; Department of Oncology, Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Zhang, Hong
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Gao, Jing-Fang
    Department of Oncology, Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Arbman, Gunnar
    Department of Oncology, Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Cao, Si-Yu-Wei
    Department of Oncology, Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Li, Yuan
    Institute of Digestive Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.
    Zhou, Zong-Guang
    Institute of Digestive Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.
    Sun, Xiao-Feng
    Department of Oncology, Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Prognostic Heterogeneity of MRE11 Based on the Location of Primary Colorectal Cancer Is Caused by Activation of Different Immune Signals2020Ingår i: Frontiers in Oncology, ISSN 2234-943X, E-ISSN 2234-943X, Vol. 9, artikel-id 1465Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: MRE11 plays an important role in DNA damage response for the maintenance of genome stability, and is becoming a prognostic marker for cancers, including colorectal cancer (CRC). However, the correlations of MRE11 to prognosis and tumor-infiltrating inflammatory cells (TIICs) in different locations of CRC remains unclear.

    Methods: Among Swedish and TCGA-COREAD patients, we investigated the association of MRE11 expression, tumor-infiltrating inflammatory cells (TIICs) and microsatellite status with survival in right-sided colon cancer (RSCC) and left-sided colon and rectal cancer (LSCRC). The signaling of MRE11-related was further analyzed using weighted gene co-expression network analysis and ClueGO.

    Results: High MRE11 expression alone or combination of high MRE11 expression with high TIICs was related to favorable prognosis in LSCRC. Moreover, high MRE11 expression was associated with favorable prognosis in LSCRC with microsatellite stability. The relationships above were adjusted for tumor stage, differentiation, and/or TIICs. However, no such evidence was observed in RSCC. Several signaling pathways involving MRE11 were found to be associated with cell cycle and DNA repair in RSCC and LSCRC, whereas, the activation of the immune response and necrotic cell death were specifically correlated with LSCRC.

    Conclusions: High MRE11 expression is an independent prognostic marker in LSCRC and enhanced prognostic potency of combining high MRE11 with high TIICs in LSCRC, mainly due to differential immune signaling activated by MRE11 in RSCC and LSCRC, respectively.

  • 5.
    Fan, Chuanwen
    et al.
    Linköping University, Linköping, Sweden.
    Kopsida, Maria
    Linköping University, Linköping, Sweden.
    Liu, Youbin
    Linköping University, Linköping, Sweden.
    Zhang, Hong
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Gao, Jingfang
    Linköping University, Linköping, Sweden.
    Arbman, Gunnar
    Linköping University, Linköping, Sweden.
    Cao, Siyuwei
    Linköping University, Linköping, Sweden.
    Li, Yuan
    West China Hospital, Sichuan University, ChengDu City, China.
    Zhou, Zongguang
    West China Hospital, Sichuan University, ChengDu City, China.
    Sun, Xiaofeng
    Linköping University, Linköping, Sweden.
    The clinical significance of MRE11 expression based on location of primary tumor in colorectal cancer patients: an integrative analysis of multi-center data2019Ingår i: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 79, nr 13Artikel i tidskrift (Övrigt vetenskapligt)
  • 6.
    Gnosa, S.
    et al.
    County Council of Östergötland, Linköping, Sweden; University of Linköping, Linköping, Sweden.
    Zhang, Hong
    Örebro universitet, Institutionen för läkarutbildning.
    Brodin, V. P.
    County Council of Östergötland, Linköping, Sweden; University of Linköping, Linköping, Sweden.
    Carstensen, J.
    Linköping University, Linköping, Sweden.
    Adell, G.
    Karolinska University Hospital, Stockholm, Sweden.
    Sun, X.-F.
    County Council of Östergötland, Linköping, Sweden; University of Linköping, Linköping, Sweden.
    AEG-1 expression is an independent prognostic factor in rectal cancer patients with preoperative radiotherapy: a study in a Swedish clinical trial2014Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 111, nr 1, s. 166-173Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Preoperative radiotherapy (RT) is widely used to downstage rectal tumours, but the rate of recurrence varies significantly. Therefore, new biomarkers are needed for better treatment and prognosis. It has been shown that astrocyte elevated gene-1 (AEG-1) is a key mediator of migration, invasion, and treatment resistance. Our aim was to analyse the AEG-1 expression in relation to RT in rectal cancer patients and to test its radiosensitising properties.

    Methods: The AEG-1 expression was examined by immunohistochemistry in 158 patients from the Swedish clinical trial of RT. Furthermore, we inhibited the AEG-1 expression by siRNA in five colon cancer cell lines and measured the survival after irradiation by colony-forming assay.

    Results: The AEG-1 expression was increased in the primary tumours compared with the normal mucosa independently of the RT (P<0.01). High AEG-1 expression in the primary tumour of the patients treated with RT correlated independently with higher risk of distant recurrence (P = 0.009) and worse disease-free survival (P = 0.007). Downregulation of AEG-1 revealed a decreased survival after radiation in radioresistant colon cancer cell lines.

    Conclusions: The AEG-1 expression was independently related to distant recurrence and disease-free survival in rectal cancer patients with RT and could therefore be a marker to discriminate patients for distant relapse.

  • 7.
    Gnosa, Sebastian
    et al.
    Linköping University, Linköping, Sweden.
    Brodin, Veronika Patcha
    Linköping University, Linköping, Sweden.
    Ticha, Ivana
    Linköping University, Linköping, Sweden.
    Adell, Gunnar
    Linköping University, Linköping, Sweden.
    Arbman, Gunnar
    Vrinnevi Hospital, Norrköping, Sweden.
    Zhang, Hong
    Örebro universitet, Institutionen för läkarutbildning.
    Sun, Xiao-Feng
    Linköping University, Linköping, Sweden.
    Genetic variants and expression of AEG-1 in relation to clinical outcome and radiotherapy response in colorectal cancer patients and cell lines2014Ingår i: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 74, nr 19Artikel i tidskrift (Övrigt vetenskapligt)
  • 8.
    Han, Shuangshuang
    et al.
    Departments of Endoscopy Center, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
    Jiang, Xia
    Departments of General Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
    Sun, Xiao-Feng
    Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Zhang, Hong
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Li, Chao
    Departments of Endoscopy Center, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
    Zhao, Zengren
    Departments of General Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
    Yu, Weifang
    Departments of Endoscopy Center, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
    Application value of CyTOF 2 mass cytometer technology at single-cell level in human gastric cancer cells2019Ingår i: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 384, nr 1, artikel-id 111568Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Chemotherapy and radiotherapy are main adjuvant therapies for the treatment of gastric cancer, the treatment effects are individual difference, but the specific mechanism is unknown. CyTOF 2 mass cytometer (CyTOF) enables the detecting up to 135 parameters on single cell, the emergence of which is an opportunity for proteomics research. We first tried to apply CyTOF technique to gastric cancer cells. We verified applicability of CyTOF in gastric cancer cells, and analyzed the responses of seventeen proteins to chemoradiotherapy in human gastric cancer AGS cells. To analyze the high dimensional CyTOF data, we used two statistical and visualization tools including viSNE and Citrus. Two specific clusters were found which had differences in protein expression profiles. CyTOF technology is proved feasibility and value at single cell level of gastric cancer.

  • 9.
    Lööf, Jasmine
    et al.
    University of Skövde, Skövde, Sweden.
    Pfeifer, Daniella
    Linköping University, Linköping, Sweden.
    Ding, Zhenyu
    Linköping University, Linköping, Sweden.
    Sun, Xiao-Feng
    Linköping University, Linköping, Sweden.
    Zhang, Hong
    University of Skövde, Skövde, Sweden.
    Effects of ΔNp73β on cisplatin treatment in colon cancer cells2012Ingår i: Molecular Carcinogenesis, ISSN 0899-1987, E-ISSN 1098-2744, Vol. 51, nr 8, s. 628-35Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    p73 can activate transcription of p53-responsive genes, thereby inhibiting cell growth. An alternative promoter in the TP73 gene gives rise to an N-terminally truncated isoform of p73, ΔNp73, which lacks the transactivation domain of the full length TAp73 protein. TAp73 is considered pro-apoptotic, and ΔNp73 anti-apoptotic. In this study, we overexpressed ΔNp73β in p53 wild type and p53 mutant colon cancer cell lines and further exposed the cells to cancer therapeutic drug cisplatin. The results showed that cisplatin decreased the protein expression levels of ΔNp73β in a dose-dependent manner, and both TAp73 and p53 were upregulated after cisplatin treatment. Further, clonogenic potential and cell viability were decreased, and apoptotic cells increased, in p53 mutant and in p53 wild type cells. Cellular viability was significantly higher in ΔNp73β-cells than mock-transfected cells. However, ΔNp73β overexpression did not affect the cellular susceptibility to cisplatin. In conclusion, the overexpression of ΔNp73β increases viability in p53 wild type and p53 mutant colon cancer cells, and cisplatin induces the degradation of ΔNp73β in a dose-dependent manner.

  • 10.
    Meng, Wen-Jian
    et al.
    Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China; Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Pathak, Surajit
    Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Ding, Zhen-Yu
    Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
    Zhang, Hong
    Örebro universitet, Institutionen för läkarutbildning.
    Adell, Gunnar
    Department of Oncology, County Council of Östergötland, Linköping, Sweden.
    Holmlund, Birgitta
    Department of Oncology, County Council of Östergötland, Linköping, Sweden.
    Li, Yuan
    Institute of Digestive Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
    Zhou, Zong-Guang
    Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China; Institute of Digestive Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
    Sun, Xiao-Feng
    Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Institute of Digestive Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
    Special AT-rich sequence binding protein 1 expression correlates with response to preoperative radiotherapy and clinical outcome in rectal cancer2015Ingår i: Cancer Biology & Therapy, ISSN 1538-4047, E-ISSN 1555-8576, Vol. 16, nr 12, s. 1738-1745Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Our recent study showed the important role of special AT-rich sequence binding protein 1 (SATB1) in the progression of human rectal cancer. However, the value of SATB1 in response to radiotherapy (RT) for rectal cancer hasn't been reported so far. Here, SATB1 was determined using immunohistochemistry in normal mucosa, biopsy, primary cancer, and lymph node metastasis from 132 rectal cancer patients: 66 with and 66 without preoperative RT before surgery. The effect of SATB1 knockdown on radiosensitivity was assessed by proliferation-based assay and clonogenic assay. The results showed that SATB1 increased from normal mucosa to primary cancer, whereas it decreased from primary cancer to metastasis in non-RT patients. SATB1 decreased in primary cancers after RT. In RT patients, positive SATB1 was independently associated with decreased response to preoperative RT, early time to metastasis, and worse survival. SATB1 negatively correlated with ataxia telangiectasia mutated (ATM) and pRb2/p130, and positively with Ki-67 and Survivin in RT patients, and their potential interaction through different canonical pathways was identified in network ideogram. Taken together, our findings disclose for the first time that radiation decreases SATB1 expression and sensitizes cancer cells to confer clinical benefit of patients, suggesting that SATB1 is predictive of response to preoperative RT and clinical outcome in rectal cancer.

  • 11.
    Meng, Wen-Jian
    et al.
    Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China.
    Yang, Lie
    Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China.
    Ma, Qin
    Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China.
    Zhang, Hong
    Örebro universitet, Institutionen för läkarutbildning.
    Adell, Gunnar
    Department of Oncology, County Council of Ostergötland, Linköping, Sweden.
    Arbman, Gunnar
    Department of Surgery, Vrinnevi Hospital, University of Linköping, Norrköping, Sweden.
    Wang, Zi-Qiang
    Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China.
    Li, Yuan
    State Key Lab Biotherapy, Inst Digest Surg, West China Hosp, Sichuan Univ, Chengdu, Peoples R China; Ctr Canc, West China Hosp, Sichuan Univ, Chengdu, Peoples R China.
    Zhou, Zong-Guang
    Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China; State Key Lab Biotherapy, Inst Digest Surg, West China Hosp, Sichuan Univ, Chengdu, Peoples R China; Ctr Canc, West China Hosp, Sichuan Univ, Chengdu, Peoples R China.
    Sun, Xiao-Feng
    State Key Lab Biotherapy, Inst Digest Surg, West China Hosp, Sichuan Univ, Chengdu, Peoples R China; Ctr Canc, West China Hosp, Sichuan Univ, Chengdu, Peoples R China; Department of Oncology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    MicroRNA Expression Profile Reveals miR-17-92 and miR-143-145 Cluster in Synchronous Colorectal Cancer2015Ingår i: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 94, nr 32Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The expression of abnormal microRNA (miRNA, miR) is a ubiquitous feature of colorectal cancer (CRC). The pathological features and clinical behaviors of synchronous CRC have been comprehensively described; however, the expression profile of miRNA and small nucleolar RNA (snoRNA) in synchronous CRC has not been elucidated. In the present study, the expression profile of miRNA and snoRNA in 5 synchronous CRCs, along with the matched normal colorectal tissue was evaluated by microarray. Function and pathway analyses of putative targets, predicted from miRNA-mRNA interaction, were performed. Moreover, we analyzed clinicopathological and molecular characteristics of 22 patients with synchronous CRC and 579 solitary CRCs in a retrospective cohort study. We found a global dysregulation of miRNAs, including an oncogenic miR-17-92 cluster and oncosuppressive miR-143-145 cluster, and snoRNAs in synchronous CRC. Differential miRNA rather than snoRNA expression was robust enough to distinguish synchronous cancer from normal mucosa. Function analysis of putative targets suggested that miRNA clusters may modulate multiple effectors of oncogenic pathways involved in the pathogenesis of synchronous CRC. A comparison of normal mucosa between synchronous and solitary CRC suggested a differential genetic background of synchronous CRC from solitary CRC during carcinogenesis. Compared with solitary cancer patients, synchronous cases exhibited multiple extra-colonic cancers (P=0.012), coexistence of adenoma (P=0.012), microsatellite instability (P=0.024), and less glucose transporter 1 (P=0.037). Aberrant miRNA expression profiles could potentially be used as a diagnostic tool for synchronous CRC. Our findings represent the first comprehensive miRNA and snoRNA expression signatures for synchronous CRC, implicating that the miRNAs and snoRNAs may present therapeutic targets for synchronous CRC.

  • 12.
    Pathak, Surajit
    et al.
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Meng, Wen-Jian
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden; West China Hospital, Sichuan University, Chengdu, China.
    Zhang, Hong
    Örebro universitet, Institutionen för läkarutbildning.
    Gnosa, Sebastian
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Nandy, Suman Kumar
    Kalyani University, Kalyani, India.
    Adell, Gunnar
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Holmlund, Birgitta
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Sun, Xiao-Feng
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Tafazzin Protein Expression Is Associated with Tumorigenesis and Radiation Response in Rectal Cancer: A Study of Swedish Clinical Trial on Preoperative Radiotherapy2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 5, artikel-id e98317Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Tafazzin (TAZ), a transmembrane protein contributes in mitochondrial structural and functional modifications through cardiolipin remodeling. TAZ mutations are associated with several diseases, but studies on the role of TAZ protein in carcinogenesis and radiotherapy (RT) response is lacking. Therefore we investigated the TAZ expression in rectal cancer, and its correlation with RT, clinicopathological and biological variables in the patients participating in a clinical trial of preoperative RT.

    Methods: 140 rectal cancer patients were included in this study, of which 65 received RT before surgery and the rest underwent surgery alone. TAZ expression was determined by immunohistochemistry in primary cancer, distant, adjacent normal mucosa and lymph node metastasis. In-silico protein-protein interaction analysis was performed to study the predictive functional interaction of TAZ with other oncoproteins.

    Results: TAZ showed stronger expression in primary cancer and lymph node metastasis compared to distant or adjacent normal mucosa in both non-RT and RT patients. Strong TAZ expression was significantly higher in stages I-III and non-mucinious cancer of non-RT patients. In RT patients, strong TAZ expression in biopsy was related to distant recurrence, independent of gender, age, stages and grade (p = 0.043, HR, 6.160, 95% CI, 1.063-35.704). In silico protein-protein interaction study demonstrated that TAZ was positively related to oncoproteins, Livin, MAC30 and FXYD-3.

    Conclusions: Strong expression of TAZ protein seems to be related to rectal cancer development and RT response, it can be a predictive biomarker of distant recurrence in patients with preoperative RT.

  • 13.
    Pham, Tuan D
    et al.
    Department of Biomedical Engineering, Linköping University, Linköping, Sweden; The Center for Artificial Intelligence, Prince Mohammad Bin Fahd University, Al Khobar, Saudi Arabia.
    Fan, Chuanwen
    Department of Oncology, Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Institute of Digestive Surgery, West China Hospital, Sichuan University, Chengdu, China.
    Pfeifer, Daniella
    Department of Oncology, Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Zhang, Hong
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Sun, Xiao-Feng
    Department of Oncology, Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Image-Based Network Analysis of DNp73 Expression by Immunohistochemistry in Rectal Cancer Patients2020Ingår i: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, artikel-id 1551Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Rectal cancer is a disease characterized with tumor heterogeneity. The combination of surgery, radiotherapy, and chemotherapy can reduce the risk of local recurrence. However, there is a significant difference in the response to radiotherapy among rectal cancer patients even they have the same tumor stage. Despite rapid advances in knowledge of cellular functions affecting radiosensitivity, there is still a lack of predictive factors for local recurrence and normal tissue damage. The tumor protein DNp73 is thought as a biomarker in colorectal cancer, but its clinical significance is still not sufficiently investigated, mainly due to the limitation of human-based pathology analysis. In this study, we investigated the predictive value of DNp73 in patients with rectal adenocarcinoma using image-based network analysis.

    Methods: The fuzzy weighted recurrence network of time series was extended to handle multi-channel image data, and applied to the analysis of immunohistochemistry images of DNp73 expression obtained from a cohort of 25 rectal cancer patients who underwent radiotherapy before surgery. Two mathematical weighted network properties, which are the clustering coefficient and characteristic path length, were computed for the image-based networks of the primary tumor (obtained after operation) and biopsy (obtained before operation) of each cancer patient.

    Results: The ratios of two weighted recurrence network properties of the primary tumors to biopsies reveal the correlation of DNp73 expression and long survival time, and discover the non-effective radiotherapy to a cohort of rectal cancer patients who had short survival time.

    Conclusion: Our work contributes to the elucidation of the predictive value of DNp73 expression in rectal cancer patients who were given preoperative radiotherapy. Mathematical properties of fuzzy weighted recurrence networks of immunohistochemistry images are not only able to show the predictive factor of DNp73 expression in the patients, but also reveal the identification of non-effective application of radiotherapy to those who had poor overall survival outcome.

  • 14.
    Song, Guohe
    et al.
    Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China.
    Xu, Shifeng
    Department of General Surgery, Shandong Provincial Hospital, Shandong University, Jinan, People’s Republic of China.
    Zhang, Hong
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Wang, Yupeng
    Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China.
    Xiao, Chao
    Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China.
    Jiang, Tao
    Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China.
    Wu, Leilei
    School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, People’s Republic of China.
    Zhang, Tao
    Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China.
    Sun, Xing
    Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China.
    Zhong, Lin
    Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China.
    Zhou, Chongzhi
    Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China.
    Wang, Zhaowen
    Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China.
    Peng, Zhihai
    Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China.
    Chen, Jian
    Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China.
    Wang, Xiaoliang
    Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China.
    TIMP1 is a prognostic marker for the progression and metastasis of colon cancer through FAK-PI3K/AKT and MAPK pathway2016Ingår i: Journal of Experimental & Clinical Cancer Research, ISSN 1756-9966, E-ISSN 1756-9966, Vol. 35, nr 1, artikel-id 148Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Tissue inhibitor matrix metalloproteinase 1 (TIMP1) plays a vital role in carcinogenesis, yet its precise functional roles and regulation remain unclear. In this study, we aim to investigate its biological function and clinical significance in human colon cancer.

    Methods: We analyzed the expression of TIMP1 in both public database (Oncomine and TCGA) and 94 cases of primary colon cancer and matched normal colon tissue specimens. The underlying mechanisms of altered TIMP1 expression on cell tumorigenesis, proliferation, and metastasis were explored in vitro and in vivo.

    Results: TIMP1 was overexpressed in colon tumorous tissues and lymph node metastasis specimens than in normal tissues. The aberrant expression of TIMP1 was significantly associated with the regional lymph node metastasis (p = 0.033), distant metastasis (p = 0.039), vascular invasion (p = 0.024) and the American Joint Committee on Cancer (AJCC) stage (p = 0.026). Cox proportional hazards model showed that TIMP1 was an independent prognostic indicator of disease-free survival (HR = 2.603, 95 % CI: 1.115-6.077, p = 0.027) and overall survival (HR = 2.907, 95 % CI: 1.254-6.737, p = 0.013) for patients with colon cancer. Consistent with this, our findings highlight that suppression of TIMP1 expression decreased proliferation, and metastasis but increased apoptosis by inducing TIMP1 specific regulated FAK-PI3K/AKT and MAPK pathway.

    Conclusion: TIMP1 might play an important role in promoting tumorigenesis and metastasis of human colon cancer and function as a potential prognostic indicator for colon cancer.

  • 15.
    Wang, Chao-Jie
    et al.
    Department of Oncology, Henan Provincial People's Hospital & People's Hospital of Henan University, Zhengzhou, Henan, P.R. China; Department of Oncology, Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Chao, Chu-Rui
    Department of Oncology, Henan Provincial People's Hospital & People's Hospital of Henan University, Zhengzhou, Henan, P.R. China.
    Liu, Hui-Min
    Department of Oncology, Henan Provincial People's Hospital & People's Hospital of Henan University, Zhengzhou, Henan, P.R. China.
    Zhu, Yan-Yan
    Department of Oncology, Henan Provincial People's Hospital & People's Hospital of Henan University, Zhengzhou, Henan, P.R. China.
    Adell, Gunnar
    Department of Oncology, Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Jarlsfelt, Ingvar
    Department of Pathology, Ryhov Hospital, Jönköping, Sweden.
    Zhang, Hong
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Sun, Xiao-Feng
    Department of Oncology, Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Prognostic value of nuclear FBI-1 in patients with rectal cancer with or without preoperative radiotherapy2019Ingår i: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 18, nr 5, s. 5301-5309Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Factor that binds to the inducer of short transcripts of the human immunodeficiency virus-1 (FBI-1) represents as a crucial gene regulator in colorectal cancer; however, the correlation between FBI-1 and preoperative radiotherapy (RT) in rectal cancer (RC) has not yet been reported. The aim was to detect FBI-1 expression in patients with RC with or without RT, by immunohistochemistry and quantitative polymerase chain reaction, and to analyze its association with clinicopathological features and response to RT. The results from immunohistochemistry analysis (n=139) and reverse transcription-quantitative polymerase chain reaction (n=55) demonstrated that FBI-1 was overexpressed in patients with RC, whether they had received preoperative RT or not. Subsequently, the association between FBI-1 expression, and the clinicopathological features and response to RT in patients with RC was analyzed. Cytoplasmic FBI-1 was upregulated in non-RT (n=77) and RT (n=62) groups (17.7 vs. 74.0%, P<0.001; 41.1 vs. 69.4%, P=0.002, respectively) of patients with RC compared with normal mucosa. However, nuclear FBI-1 was downregulated (75.8 vs. 22.1%, P<0.001; 83.9 vs. 35.5%, P<0.001, respectively) in both groups. RT had no significant effect on FBI-1 expression in RC tissues. Furthermore, nuclear FBI-1 was positively associated with tumor-node-metastasis stage and distant recurrence (P=0.003 and P=0.010, respectively). In patients with stage I, II or III RC, higher nuclear FBI-1 expression was associated with poorer disease-free survival [hazard ratio (HR)=1.934, 95% confidence interval (CI): 1.055-3.579, P=0.033] and overall survival (HR=2.174, 95% CI: 1.102-4.290, P=0.025), independently of sex, age, growth pattern, differentiation and RT. In addition, FBI-1 was positively correlated with numerous biological factors, including p73 [Spearman's correlation coefficient (rs)=0.332, P=0.007], lysyl oxidase (rs=0.234, P=0.043), Wrap53 (rs=-0.425, P=0.0002) and peroxisome proliferator-activated receptor δ (rs=-0.294, P=0.026). In conclusion, the present study demonstrated that nuclear FBI-1 was an independent prognostic factor in patients with RC and correlated with numerous biological factors, which indicated that it may have multiple roles in RC.

  • 16.
    Wang, Chao-Jie
    et al.
    Dept Oncolgy, Henan Province Peoples Hospital, Zhengzhou University, Zhengzhou, Peoples R China.; Fac Hlth Sci, Div Oncol, Dept Clin & Experimental Medicine, Linköping University, Linköping, Sweden.
    Frayennbergh-Karlson, Hanna
    Fac Health Science, Div Oncology, Dept Clin & Experimental Med, Linköping University, Linköping, Sweden..
    Wang, Da-Wei
    Dept Stomatol, Hosp 1, Hebei Medical University, Shijiazhuang, Peoples R China.
    Arbman, Gunnar
    Dept Surg, Vrinnevi Hospital, Linköping University, Norrköping, Sweden.
    Zhang, Hong
    Örebro universitet, Institutionen för läkarutbildning.
    Sun, Xiao-Feng
    Fac Health Science, Div Oncology, Dept Clin & Experimental Medicine , City Council Östergötland, Linköping University, Linköping, Sweden.
    Clinicopathological significance of BTF3 expression in colorectal cancer2013Ingår i: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 34, nr 4, s. 2141-2146Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Basic transcription factor 3 (BTF3) is a general RNA polymerase II transcription factor and is also involved in apoptosis regulation. Increasing evidence shows that BTF3 is aberrantly expressed in several kinds of malignancies, but there is no study to analyze BTF3 expression in colorectal cancer (CRC) patients. Applying immunohistochemistry, we detected BTF3 in CRCs (n = 156), the corresponding distant (n = 42), adjacent normal mucosa (n = 96), lymph node metastases (n = 35), and analyzed its relationships with clinicopathological and biological variables. Our results showed that BTF3 staining significantly increased from distant or adjacent normal mucosa to primary CRCs (p < 0.0001) or metastases (p = 0.002 and p < 0.0001). BTF3 was higher in distal cancers than in proximal cancers (57 % vs. 39 %, p = 0.041). It also showed stronger staining in primary CRCs stage I and II than that in stage III and IV (64 % vs. 35 %, p = 0.0004), or metastases (64 % vs. 29 %, p = 0.004). Cancers with better differentiation had a higher expression than those with worse differentiation (56 % vs. 37 %, p = 0.031). There were positive correlations of BTF3 expression with nuclear factor kappa B (NF-kappa B), RAD50, MRE11, NBS1, and AEG-1 (p < 0.05). In conclusion, BTF3 overexpression may be an early event in CRC development and could be useful biomarker for the early stage of CRCs. BTF3 has positive correlations with NF-kappa B, RAD50, MRE11, NBS1 and AEG-1, and might influence complex signal pathways in CRC.

  • 17.
    Wang, Chao-Jie
    et al.
    Department of Oncology, Henan Provincial People’s Hospital & People’s Hospital of Henan University, Zheng-zhou, China; Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Zhou, Jian-Wei
    Department of Oncology, Henan Provincial People’s Hospital & People’s Hospital of Henan University, Zheng-zhou, China.
    Cheng, Qiao-Mei
    Department of Oncology, Henan Provincial People’s Hospital & People’s Hospital of Henan University, Zheng-zhou, China.
    Zhou, Yun
    Department of Oncology, Henan Provincial People’s Hospital & People’s Hospital of Henan University, Zheng-zhou, China.
    Zhang, Hong
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Sun, Xiao-Feng
    Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    FBI-1 mRNA in normal mucosa is an independent prognostic factor in colorectal cancer patients2018Ingår i: International Journal of Clinical and Experimental Pathology, ISSN 1936-2625, E-ISSN 1936-2625, Vol. 11, nr 2, s. 642-649Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Although several studies provide evidence that FBI-1 is an important gene regulator in colorectal cancer (CRC), it is noteworthy that, to our knowledge, no analysis of the correlation between FBI-1 expression and prognosis in CRC has been reported. Using real-time RT-PCR, we detected FBI-1 mRNA in 161 CRC patients (primary tumor, along with the corresponding normal mucosa), 36 liver metastases, and analyzed the relationship of its expression with clinicopathological features. Colon cancer cell lines were used to study FBI-1 function. Our study found that FBI-1 was significant up-regulated in tumor tissue (2.621 +/- 0.157) compared with the corresponding normal mucosa (1.620 +/- 0.165, P < 0.0001). FBI-1 in normal mucosa was a prognostic factor (P = 0.039, RR 0.431, 95% CI 0.194-0.958), independent of gender, age, stage, and differentiation. High levels of FBI-1 mRNA were related with good survival. Patients with complications had a higher primary tumor FBI-1 expression than those without complications (3.400 +/- 0.332 vs. 2.516 +/- 0.241, P = 0.032). Suppression of FBI-1 in colon cancer cell lines could repress proliferation of cancer cells. In conclusion, FBI-1 mRNA is overexpressed in CRC, and takes part in the development of CRC. FBI-1 mRNA in normal mucosa is an independent prognostic factor. Our findings give further support to the concept of "field cancerization", and hint that when we study a biomarker, we should not only focus on the tumor tissue but also the corresponding normal mucosa.

  • 18.
    Wang, Mo-Jin
    et al.
    Sichuan University, Chengdu, China; Linköping University, Linköping, Sweden.
    Ping, Jie
    Linköping University, Linköping, Sweden.
    Li, Yuan
    Sichuan University, Chengdu, China.
    Adell, Gunnar
    Linköping University, Linköping, Sweden.
    Arbman, Gunnar
    Linköping University, Linköping, Sweden.
    Nodin, Bjorn
    Lund University, Lund, Sweden.
    Meng, Wen-Jian
    Sichuan University, Chengdu, China; Linköping University, Linköping, Sweden.
    Zhang, Hong
    Örebro universitet, Institutionen för läkarutbildning.
    Yu, Yong-Yang
    Sichuan University, Chengdu, China.
    Wang, Cun
    Sichuan University, Chengdu, China.
    Yang, Lie
    Sichuan University, Chengdu, China.
    Zhou, Zong-Guang
    Sichuan University, Chengdu, China.
    Sun, Xiao-Feng
    Sichuan University, Chengdu, China; Linköping University, Linköping, Sweden.
    The prognostic factors and multiple biomarkers in young patients with colorectal cancer2015Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, artikel-id 10645Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The incidence of colorectal cancer (CRC) in young patients (<= 50 years of age) appears to be increasing. However, their clinicopathological characteristics and survival are controversial. Likewise, the biomarkers are unclear. We used the West China (2008-2013, China), Surveillance, Epidemiology, and End Results program (1973-2011, United States) and Linkoping Cancer (1972-2009, Sweden) databases to analyse clinicopathological characteristics, survival and multiple biomarkers of young CRC patients. A total of 509,934 CRC patients were included from the three databases. The young CRC patients tended to have more distal location tumours, fewer tumour numbers, later stage, more mucinous carcinoma and poorer differentiation. The cancer-specific survival (CSS) of young patients was significantly better. The PRL (HR = 12.341, 95% CI = 1.615-94.276, P = 0.010), RBM3 (HR = 0.093, 95% CI = 0.012-0.712, P = 0.018), Wrap53 (HR = 1.952, 95% CI = 0.452-6.342, P = 0.031), p53 (HR = 5.549, 95% CI = 1.176-26.178, P = 0.045) and DNA status (HR = 17.602, 95% CI = 2.551-121.448, P = 0.001) were associated with CSS of the young patients. In conclusion, this study suggests that young CRC patients present advanced tumours and more malignant pathological features, while they have a better prognosis. The PRL, RBM3, Wrap53, p53 and DNA status are potential prognostic biomarkers for the young CRC patients.

  • 19.
    Wang, Mo-Jin
    et al.
    Department of Gastrointestinal Surgery, Institute of Digestive Surgery and State key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; Department of Oncology, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Ping, Jie
    Department of Oncology, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Li, Yuan
    Department of Paediatric Surgery, Institute of Digestive Surgery and State key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
    Holmqvist, Annica
    Department of Oncology, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Adell, Gunnar
    Department of Oncology, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Arbman, Gunnar
    Department of Oncology, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Zhang, Hong
    Örebro universitet, Institutionen för läkarutbildning.
    Zhou, Zong-Guang
    Department of Gastrointestinal Surgery, Institute of Digestive Surgery and State key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
    Sun, Xiao-Feng
    Department of Gastrointestinal Surgery, Institute of Digestive Surgery and State key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; Department of Oncology, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Prognostic significance and molecular features of colorectal mucinous adenocarcinomas: A strobe-compliant study2015Ingår i: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 94, nr 51, artikel-id e2350Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mucinous adenocarcinoma (MC) is a special histology subtype of colorectal adenocarcinoma. The survival of MC is controversial and the prognostic biomarkers of MC remain unclear. To analyze prognostic significance and molecular features of colorectal MC. This study included 755,682 and 1001 colorectal cancer (CRC) patients from Surveillance, Epidemiology, and End Results program (SEER, 1973 2011), and Linkoping Cancer (LC, 1972-2009) databases. We investigated independently the clinicopathological characteristics, survival, and variety of molecular features from these 2 databases. MC was found in 9.3% and 9.8% patients in SEER and LC, respectively. MC was more frequently localized in the right colon compared with nonmucinous adenocarcinoma (NMC) in both SEER (57.7% vs 37.2%, P < 0.001) and LC (46.9% vs 27.7%, P < 0.001). Colorectal MC patients had significantly worse cancer-specific survival (CSS) than NMC patients (SEER, P < 0.001; LC, P = 0.026), prominently in stage III (SEER, P < 0.001; P=0.023). The multivariate survival analysis showed that MC was independently related to poor prognosis in rectal cancer patients (SEER, hazard ratios [HR], 1.076; 95% confidence intervals [CI], 1.057-1.096; P < 0.001). In LC, the integrated analysis of genetic and epigenetic features showed that that strong expression of PINCH (HR, 3.954; 95% CI, 1.493-10.47; P = 0.013) and weak expression of RAD50 (HR 0.348, 95% CT, 0.106-1.192; P=0.026) were significantly associated with poor CSS of colorectal MC patients. In conclusion, the colorectal MC patients had significantly worse CSS than NMC patients, prominently in stage III. MC was an independent prognostic factor associated with worse survival in rectal cancer patients. The PINCH and RAD50 were prognostic biomarkers for colorectal MC patients.

  • 20.
    Xiao, Chao
    et al.
    Department of General Surgery, Shanghai General Hospital School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
    Wang, Yupeng
    Department of General Surgery, Shanghai General Hospital School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
    Zheng, Miao
    Department of General Surgery, Shanghai General Hospital School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
    Chen, Jian
    Department of General Surgery, Shanghai General Hospital School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
    Song, Guohe
    Department of General Surgery, Shanghai General Hospital School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
    Zhou, Zhijie
    Department of General Surgery, Shanghai General Hospital School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
    Zhou, Chongzhi
    Department of General Surgery, Shanghai General Hospital School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
    Sun, Xing
    Department of General Surgery, Shanghai General Hospital School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
    Zhong, Lin
    Department of General Surgery, Shanghai General Hospital School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
    Ding, Erxun
    Department of General Surgery, Shanghai General Hospital School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
    Zhang, Yi
    Department of General Surgery, Shanghai General Hospital School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
    Yang, Liu
    Department of Obstetrics and Gynecology, Shanghai General Hospital School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
    Wu, Gang
    Department of General Surgery, Henan Provincial People's Hospital People's Hospital, Zhengzhou University, Zhengzhou, People's Republic of China.
    Xu, Shifeng
    Department of General Surgery, Shandong Provincial Hospital Affiliated, Shandong University, Jinan, People's Republic of China.
    Zhang, Hong
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Wang, Xiaoliang
    Department of General Surgery, Shanghai General Hospital School of Medicine, Jiao Tong University, Shanghai, People's Republic of China.
    RBBP6 increases radioresistance and serves as a therapeutic target for preoperative radiotherapy in colorectal cancer2018Ingår i: Cancer Science, ISSN 1347-9032, E-ISSN 1349-7006, Vol. 109, nr 4, s. 1075-1087Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Radiotherapy (RT) can be used as preoperative treatment to downstage initially unresectable locally rectal carcinoma, but the radioresistance and recurrence remain significant problems. Retinoblastoma binding protein 6 (RBBP6) has been implicated in the regulation of cell cycle, apoptosis and chemoresistance both in vitro and in vivo. This study investigated whether the inhibition of RBBP6 expression would improve radiosensitivity in human colorectal cancer cells. After SW620 and HT29 cells were exposed to radiation, the levels of RBBP6 mRNA and protein increased over time in both two cells. Moreover, a significant reduction in clonogenic survival and a decrease in cell viability in parallel with an obvious increase in cell apoptosis were demonstrated in irradiated RBBP6-knockdown cells. Besides, transfection with RBBP6 shRNA improved levels of G2-M phase arrest which blocked the cells in a more radiosensitive period of the cell cycle. These observations indicated that cell cycle and apoptosis mechanisms may be connected with tumor cell survival following radiotherapy. In vivo, tumor growth rate of nude mice in RBBP6-knockdown group was significantly slower than that in other groups. These results indicated that RBBP6 overexpression could resist colorectal cancer cells against radiation by regulating cell cycle and apoptosis pathways, and inhibition of RBBP6 could enhance radiosensitivity of human colorectal cancer.

  • 21.
    Xueli, Zhang
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Centre for Systems Biology, Soochow University, Suzhou, China.
    Sun, Xiao-Feng
    Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Cao, Yang
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Ye, Benchen
    Centre for Systems Biology, Soochow University, Suzhou, China.
    Peng, Qiliang
    Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
    Liu, Xingyun
    Centre for Systems Biology, Soochow University, Suzhou, China.
    Shen, Bairong
    Centre for Systems Biology, Soochow University, Suzhou, China.
    Zhang, Hong
    Örebro universitet, Institutionen för medicinska vetenskaper.
    CBD: a biomarker database for colorectal cancer2018Ingår i: Database: The Journal of Biological Databases and Curation, ISSN 1758-0463, E-ISSN 1758-0463, artikel-id bay046Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Colorectal cancer (CRC) biomarker database (CBD) was established based on 870 identified CRC biomarkers and their relevant information from 1115 original articles in PubMed published from 1986 to 2017. In this version of the CBD, CRC biomarker data were collected, sorted, displayed and analysed. The CBD with the credible contents as a powerful and time-saving tool provide more comprehensive and accurate information for further CRC biomarker research. The CBD was constructed under MySQL server. HTML, PHP and JavaScript languages have been used to implement the web interface. The Apache was selected as HTTP server. All of these web operations were implemented under the Windows system. The CBD could provide to users the multiple individual biomarker information and categorized into the biological category, source and application of biomarkers; the experiment methods, results, authors and publication resources; the research region, the average age of cohort, gender, race, the number of tumours, tumour location and stage. We only collect data from the articles with clear and credible results to prove the biomarkers are useful in the diagnosis, treatment or prognosis of CRC. The CBD can also provide a professional platform to researchers who are interested in CRC research to communicate, exchange their research ideas and further design high-quality research in CRC. They can submit their new findings to our database via the submission page and communicate with us in the CBD.

  • 22.
    Xueli, Zhang
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Centre for Systems Biology, Soochow University, Suzhou, China.
    Sun, Xiao-Feng
    Department of Oncology and Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Shen, Bairong
    Centre for Systems Biology, Soochow University, Suzhou, China.
    Zhang, Hong
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Potential Applications of DNA, RNA and Protein Biomarkers in Diagnosis, Therapy and Prognosis for Colorectal Cancer: A Study from Databases to AI-Assisted Verification2019Ingår i: Cancers, ISSN 2072-6694, Vol. 11, nr 2, artikel-id 172Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In order to find out the most valuable biomarkers and pathways for diagnosis, therapy and prognosis in colorectal cancer (CRC) we have collected the published CRC biomarkers and established a CRC biomarker database (CBD: http://sysbio.suda.edu.cn/CBD/index.html). In this study, we analysed the single and multiple DNA, RNA and protein biomarkers as well as their positions in cancer related pathways and protein-protein interaction (PPI) networks to describe their potential applications in diagnosis, therapy and prognosis. CRC biomarkers were collected from the CBD. The RNA and protein biomarkers were matched to their corresponding DNAs by the miRDB database and the PubMed Gene database, respectively. The PPI networks were used to investigate the relationships between protein biomarkers and further detect the multiple biomarkers. The Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Ontology (GO) annotation were used to analyse biological functions of the biomarkers. AI classification techniques were utilized to further verify the significances of the multiple biomarkers in diagnosis and prognosis for CRC. We showed that a large number of the DNA, RNA and protein biomarkers were associated with the diagnosis, therapy and prognosis in various degrees in the CRC biomarker networks. The CRC biomarkers were closely related to the CRC initiation and progression. Moreover, the biomarkers played critical roles in cellular proliferation, apoptosis and angiogenesis and they were involved in Ras, p53 and PI3K pathways. There were overlaps among the DNA, RNA and protein biomarkers. AI classification verifications showed that the combined multiple protein biomarkers played important roles to accurate early diagnosis and predict outcome for CRC. There were several single and multiple CRC protein biomarkers which were associated with diagnosis, therapy and prognosis in CRC. Further, AI-assisted analysis revealed that multiple biomarkers had potential applications for diagnosis and prognosis in CRC.

  • 23.
    Xueli, Zhang
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Centre for Systems Biology, Soochow University, Suzhou, China.
    Zhang, Hong
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Shen, Bairong
    Centre for Systems Biology, Soochow University, Suzhou, China.
    Sun, Xiao-Feng
    Department of Oncology and Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Chromogranin-A Expression as a Novel Biomarker for Early Diagnosis of Colon Cancer Patients2019Ingår i: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 20, nr 12, artikel-id 2919Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Colon cancer is one of the major causes of cancer death worldwide. The five-year survival rate for the early-stage patients is more than 90%, and only around 10% for the later stages. Moreover, half of the colon cancer patients have been clinically diagnosed at the later stages. It is; therefore, of importance to enhance the ability for the early diagnosis of colon cancer. Taking advantages from our previous studies, there are several potential biomarkers which have been associated with the early diagnosis of the colon cancer. In order to investigate these early diagnostic biomarkers for colon cancer, human chromogranin-A (CHGA) was further analyzed among the most powerful diagnostic biomarkers. In this study, we used a logistic regression-based meta-analysis to clarify associations of CHGA expression with colon cancer diagnosis. Both healthy populations and the normal mucosa from the colon cancer patients were selected as the double normal controls. The results showed decreased expression of CHGA in the early stages of colon cancer as compared to the normal controls. The decline of CHGA expression in the early stages of colon cancer is probably a new diagnostic biomarker for colon cancer diagnosis with high predicting possibility and verification performance. We have also compared the diagnostic powers of CHGA expression with the typical oncogene KRAS, classic tumor suppressor TP53, and well-known cellular proliferation index MKI67, and the CHGA showed stronger ability to predict early diagnosis for colon cancer than these other cancer biomarkers. In the protein-protein interaction (PPI) network, CHGA was revealed to share some common pathways with KRAS and TP53. CHGA might be considered as a novel, promising, and powerful biomarker for early diagnosis of colon cancer.

  • 24.
    Xueli, Zhang
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Centre for Systems Biology, Soochow University, Suzhou, China.
    Zhang, Hong
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Shen, Bairong
    Centre for Systems Biology, Soochow University, Suzhou, China.
    Sun, Xiao-Feng
    Department of Oncology and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Novel MicroRNA Biomarkers for Colorectal Cancer Early Diagnosis and 5-Fluorouracil Chemotherapy Resistance but Not Prognosis: A Study from Databases to AI-Assisted Verifications2020Ingår i: Cancers, ISSN 2072-6694, Vol. 12, nr 2, artikel-id E341Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Colorectal cancer (CRC) is one of the major causes of cancer death worldwide. In general, early diagnosis for CRC and individual therapy have led to better survival for the cancer patients. Accumulating studies concerning biomarkers have provided positive evidence to improve cancer early diagnosis and better therapy. It is, however, still necessary to further investigate the precise biomarkers for cancer early diagnosis and precision therapy and predicting prognosis. In this study, AI-assisted systems with bioinformatics algorithm integrated with microarray and RNA sequencing (RNA-seq) gene expression (GE) data has been approached to predict microRNA (miRNA) biomarkers for early diagnosis of CRC based on the miRNA-messenger RNA (mRNA) interaction network. The relationships between the predicted miRNA biomarkers and other biological components were further analyzed on biological networks. Bayesian meta-analysis of diagnostic test was utilized to verify the diagnostic value of the miRNA candidate biomarkers and the combined multiple biomarkers. Biological function analysis was performed to detect the relationship of candidate miRNA biomarkers and identified biomarkers in pathways. Text mining was used to analyze the relationships of predicted miRNAs and their target genes with 5-fluorouracil (5-FU). Survival analyses were conducted to evaluate the prognostic values of these miRNAs in CRC. According to the number of miRNAs single regulated mRNAs (NSR) and the number of their regulated transcription factor gene percentage (TFP) on the miRNA-mRNA network, there were 12 promising miRNA biomarkers were selected. There were five potential candidate miRNAs (miRNA-186-5p, miRNA-10b-5, miRNA-30e-5p, miRNA-21 and miRNA-30e) were confirmed as CRC diagnostic biomarkers, and two of them (miRNA-21 and miRNA-30e) were previously reported. Furthermore, the combinations of the five candidate miRNAs biomarkers showed better prediction accuracy for CRC early diagnosis than the single miRNA biomarkers. miRNA-10b-5p and miRNA-30e-5p were associated with the 5-FU therapy resistance by targeting the related genes. These miRNAs biomarkers were not statistically associated with CRC prognosis.

  • 25.
    Zhang, Hong
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Zhu, Zhen-Long
    Department of Pathology, The First Hospital of Hebei Medical University, Shijiazhuang, China.
    Wang, Da-Wei
    Department of Stomatology, The Third Hospital of Hebei Medical University, Shijiazhuang, China.
    Yang, Yan-Hong
    Department of Pathology, The First Hospital of Hebei Medical University, Shijiazhuang, China.
    Wang, Hao
    Department of Stomatology, The Third Hospital of Hebei Medical University, Shijiazhuang, China.
    Sun, Xiao-Feng
    Division of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, University of Linköping, Linköping, Sweden.
    Upregulation of nucleoporin 88 is associated with nodal metastasis and poor differentiation in oral squamous cell carcinoma2016Ingår i: International Journal of Clinical and Experimental Medicine, ISSN 1940-5901, E-ISSN 1940-5901, Vol. 9, nr 5, s. 8399-8404Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Nucleoporin 88 (Nup 88) is a component of the nuclear pore complexes (NPCs) that mediates nucleocytoplasmic trafficking of macromolecules, Nup 88 has been reported to be up-regulated in a wide variety of malignancies. Studies show that overexpression of this antigen is associated with the development, agressiveness, differentiation and prognosis in some tumours. Since no study has been carried out in the relationship between the Nup 88 expression and clinicopathological features in the patients with oral squamous cell carcinoma (OSCC), this study aimed to determine Nup 88 expression in OSCC and its clinicopathological significance. Nup 88 expression was examined by immunohistochemistry in 20 normal oral mucosa specimens and 83 OSCC tissues. The frequency of positive Nup 88 expression was gradually increased from normal oral mucosa (10%) to primary OSCC (40%, P=0.012). The Nup 88 positive rate in OSCC patient with nodal metastasis was significantly higher than those without nodal metastasis (64% vs. 21%, P=0.000085). The frequency of positive Nup 88 expression was significantly different between worse and better differentiation (80 vs. 27%, P=0.000024). Nup 88 expression was not related to the patients' gender, age, location and tumour size (P>0.05). In conclusion, Nup 88 may play an important role in tumorigenesis in oral squamous cell carcinoma. Upregulation of Nup 88 is associated with nodal metastasis and poor differentiation in oral squamous cell carcinoma.

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