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Ugge, H., Downer, M. K., Carlsson, J., Bowden, M., Davidsson, S., Mucci, L. A., . . . Andrén, O. (2019). Circulating inflammation markers and prostate cancer. The Prostate, 79(11), 1338-1346
Open this publication in new window or tab >>Circulating inflammation markers and prostate cancer
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2019 (English)In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 79, no 11, p. 1338-1346Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Chronic inflammation is thought to influence the risk of prostate cancer. The purpose of this population-based case-control study was to evaluate the association of 48 circulating inflammation markers with prostate cancer, to identify candidate markers for further investigation.

METHODS: Serum samples collected from 235 prostate cancer patients and 198 population-based controls recruited in Örebro County, Sweden, in 1989-1991, were assessed using a multiplex bead-based immunoassay to determine concentrations of 48 circulating inflammation markers. Logistic regression was first used to evaluate the association between individual markers (highest vs lowest concentration quartile) and prostate cancer in unadjusted and mutually adjusted models. Second, patients with inflammatory conditions, metastatic or advanced prostate cancer, were excluded to address the possible influence of systemic disease on inflammation markers.

RESULTS: Individual analyses first identified 21 markers associated with prostate cancer (P < .05), which after mutual adjustment were reduced to seven markers. After the exclusion of men with conditions linked with systemic inflammation, associations between prostate cancer and deviant levels of C-X3-C motif chemokine ligand 1, platelet-derived growth factor subunit B homodimer, interleukin 10, C-C motif chemokine ligand (CCL) 21, and CCL11 remained statistically significant.

CONCLUSIONS: In this explorative study, we identified candidate inflammation markers of possible importance for prostate cancer pathophysiology, for further evaluation in prospective studies.

Place, publisher, year, edition, pages
Alan R. Liss Inc., 2019
Keywords
Circulating, cytokines, inflammation, markers, prostate cancer
National Category
Cancer and Oncology Urology and Nephrology
Identifiers
urn:nbn:se:oru:diva-74753 (URN)10.1002/pros.23842 (DOI)000473235500014 ()31212389 (PubMedID)2-s2.0-85068041866 (Scopus ID)
Note

Funding Agency:

Lions Cancerforskningsfond vid Akademiska sjukhuset i Uppsala. (Part of Lions International)

Available from: 2019-06-20 Created: 2019-06-20 Last updated: 2019-08-09Bibliographically approved
Zelic, R., Zugna, D., Bottai, M., Andrén, O., Fridfeldt, J., Carlsson, J., . . . Akre, O. (2019). Estimation of Relative and Absolute Risks in a Competing-Risks Setting Using a Nested Case-Control Study Design: Example From the ProMort Study. American Journal of Epidemiology, 188(6), 1165-1173
Open this publication in new window or tab >>Estimation of Relative and Absolute Risks in a Competing-Risks Setting Using a Nested Case-Control Study Design: Example From the ProMort Study
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2019 (English)In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 188, no 6, p. 1165-1173Article in journal (Refereed) Published
Abstract [en]

In this paper, we describe the Prognostic Factors for Mortality in Prostate Cancer (ProMort) study and use it to demonstrate how the weighted likelihood method can be used in nested case-control studies to estimate both relative and absolute risks in the competing-risks setting. ProMort is a case-control study nested within the National Prostate Cancer Register (NPCR) of Sweden, comprising 1,710 men diagnosed with low- or intermediate-risk prostate cancer between 1998 and 2011 who died from prostate cancer (cases) and 1,710 matched controls. Cause-specific hazard ratios and cumulative incidence functions (CIFs) for prostate cancer death were estimated in ProMort using weighted flexible parametric models and compared with the corresponding estimates from the NPCR cohort. We further drew 1,500 random nested case-control subsamples of the NPCR cohort and quantified the bias in the hazard ratio and CIF estimates. Finally, we compared the ProMort estimates with those obtained by augmenting competing-risks cases and by augmenting both competing-risks cases and controls. The hazard ratios for prostate cancer death estimated in ProMort were comparable to those in the NPCR. The hazard ratios for dying from other causes were biased, which introduced bias in the CIFs estimated in the competing-risks setting. When augmenting both competing-risks cases and controls, the bias was reduced.

Place, publisher, year, edition, pages
Oxford University Press, 2019
Keywords
absolute risk, competing risks, cumulative incidence function, flexible parametric survival model, inverse probability weighting, nested case-control studies, weighted likelihood
National Category
Cancer and Oncology Urology and Nephrology
Identifiers
urn:nbn:se:oru:diva-75236 (URN)10.1093/aje/kwz026 (DOI)000473760200020 ()30976789 (PubMedID)2-s2.0-85067089473 (Scopus ID)
Funder
Swedish Cancer Society
Available from: 2019-07-25 Created: 2019-07-25 Last updated: 2019-07-25Bibliographically approved
Carlsson, J., Vikerfors, A., Frey, J., Jerlström, T. & Davidsson, S. (2019). Is soluble PD-L1 a potential biomarker for urothelial bladder cancer?. In: : . Paper presented at Keystone Symposia Conference 2019: Cancer metastasis: The role of metabolism, immunity and the microenvironment, Florens, Italy, March 15-19, 2019.
Open this publication in new window or tab >>Is soluble PD-L1 a potential biomarker for urothelial bladder cancer?
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2019 (English)Conference paper, Oral presentation with published abstract (Refereed)
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-73843 (URN)
Conference
Keystone Symposia Conference 2019: Cancer metastasis: The role of metabolism, immunity and the microenvironment, Florens, Italy, March 15-19, 2019
Available from: 2019-04-17 Created: 2019-04-17 Last updated: 2019-04-17Bibliographically approved
Davidsson, S., Sundqvist, P., Giunchi, F., Erlandsson, A., Fiorentiono, M. & Carlsson, J. (2019). M2 macrophages and regulatory T cells as prognostic markers in renal cell carcinoma. In: : . Paper presented at Keystone Symposia Conference 2109: Cancer metastasis: The role of metabolism, immunity and the microenvironment, Florens, Italy, March 15—19, 2019.
Open this publication in new window or tab >>M2 macrophages and regulatory T cells as prognostic markers in renal cell carcinoma
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2019 (English)Conference paper, Oral presentation with published abstract (Refereed)
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-73842 (URN)
Conference
Keystone Symposia Conference 2109: Cancer metastasis: The role of metabolism, immunity and the microenvironment, Florens, Italy, March 15—19, 2019
Available from: 2019-04-17 Created: 2019-04-17 Last updated: 2019-04-17Bibliographically approved
Erlandsson, A., Carlsson, J., Lundholm, M., Fält, A., Andersson, S.-O., Andrén, O. & Davidsson, S. (2019). M2 macrophages and regulatory T cells in lethal prostate cancer. The Prostate, 79(4), 363-369
Open this publication in new window or tab >>M2 macrophages and regulatory T cells in lethal prostate cancer
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2019 (English)In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 79, no 4, p. 363-369Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Prostate cancer (PCa) is one of the most frequently diagnosed cancers in the world. Emerging evidence suggests that inflammatory cells such as M2 macrophages and regulatory T cells (Tregs) can contribute to cancer progression by suppressing the anti‐tumor immune response. This study investigated the number of CD163‐positive M2 macrophages in PCa tissue. It also investigated the correlation and interaction of M2 macrophages and Tregs.

METHODS: were assessed using Spearman's rank-order correlation and a likelihood test, respectively. Logistic regression was used to estimate odds ratios (ORs) for lethal PCa and macrophage counts.

RESULTS: showed a significant correlation (P < 0.001) but no interactions. The OR for lethal PCa was 1.93 (95%CI: 1.23-3.03) for men with high numbers of M2 macrophages. Also for cases with uncertain outcome (GS categories 3 + 4 and 4 + 3) high numbers of M2 macrophages does predict a poorer prognosis.

CONCLUSIONS: Our data showed that men with high numbers of M2 macrophages in the prostate tumor environment had increased odds of dying of PCa. It is possible that M2 macrophages, together with other suppressor cells such as Tregs , promote an immunosuppressive environment.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
CD163, FOXP3, TAMs, Tregs
National Category
Urology and Nephrology Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-70404 (URN)10.1002/pros.23742 (DOI)000456214000004 ()30500076 (PubMedID)2-s2.0-85057833977 (Scopus ID)
Available from: 2018-12-03 Created: 2018-12-03 Last updated: 2019-02-05Bibliographically approved
Davidsson, S., Carlsson, J., Giunchi, F., Harlow, A., Kirrander, P., Rider, J., . . . Andrén, O. (2019). PD-L1 Expression in Men with Penile Cancer and its Association with Clinical Outcomes. European Urology Oncology, 2(2), 214-221
Open this publication in new window or tab >>PD-L1 Expression in Men with Penile Cancer and its Association with Clinical Outcomes
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2019 (English)In: European Urology Oncology, E-ISSN 2588-9311, Vol. 2, no 2, p. 214-221Article in journal (Refereed) Published
Abstract [en]

Background: It has been hypothesized that PD-L1 expression in tumor cells and tumor-infiltrating immune (TII) cells may contribute to tumor progression by inhibiting antitumor immunity.

Objective: To investigate the association between PD-L1 expression in tumor cells and TII cells and clinical outcomes in penile cancer.

Design, setting, and participants: A cohort of 222 men treated for penile squamous cell carcinoma (SqCC) at Örebro University Hospital between 1984 and 2008 with long-term follow-up (median 34 mo) was evaluated for PD-L1 expression in tumor cells and TII cells via immunohistochemistry.

Outcome measurements and statistical analysis: Association between clinicopathological features and PD-L1 expression was estimated using χ2 and Fisher's exact tests. For survival analyses, Kaplan-Meier curves with log-rank tests and multivariate Cox proportional hazards regression models were used.

Results and limitations: We found that 32.1% of the tumors and 64.2% of the TII cells expressed PD-L1. Our data demonstrate that penile SqCC patients with PD-L1–positive tumor cells or TII cells are at significant risk of lower cancer-specific survival and that the prognostic value of PD-L1 expression was strongest for tumor cell positivity. The use of tissue microarrays rather than whole sections may be viewed as a limitation.

Conclusions: Tumor PD-L1 expression independently identifies penile SqCC patients at risk of poor clinical outcomes.

Patient summary: We investigated how many patients with penile cancer had tumors that manufactured PD-L1, a protein that decreases the ability of the immune system to fight cancer. We found that up to one-third of penile tumors make this protein. Patients whose tumors make PD-L1 have more aggressive penile cancer and worse clinical outcomes.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Penile squamos cell carcinoma, Immunohistochemistry, PD-L1
National Category
Urology and Nephrology Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-73687 (URN)10.1016/j.euo.2018.07.010 (DOI)000474610700014 ()31017099 (PubMedID)2-s2.0-85065334391 (Scopus ID)
Available from: 2019-04-12 Created: 2019-04-12 Last updated: 2019-07-29Bibliographically approved
Carlsson, J., Sundqvist, P., Kosuta, V., Fält, A., Giunchi, F., Fiorentino, M. & Davidsson, S. (2019). PD-L1 Expression is Associated With Poor Prognosis in Renal Cell Carcinoma. Applied immunohistochemistry & molecular morphology (Print)
Open this publication in new window or tab >>PD-L1 Expression is Associated With Poor Prognosis in Renal Cell Carcinoma
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2019 (English)In: Applied immunohistochemistry & molecular morphology (Print), ISSN 1541-2016, E-ISSN 1533-4058Article in journal (Refereed) Epub ahead of print
Abstract [en]

Programmed death ligand 1 (PD-L1) is a protein which, when interacting with its receptor programmed death 1, acts as a negative regulator of the antitumor T-cell-mediated immune response. The prognostic value of PD-L1 expression in renal cell carcinoma (RCC) has been controversial. In this study, the prognostic value of PD-L1 expression in RCC was evaluated by analyzing PD-L1 immunoreactivity in tumor cells and tumor-infiltrating immune cells (TIICs) in 346 RCC patients with long-term follow-up. PD-L1 positivity in tumor cells was associated with higher World Health Organization nucleolar grade (P<0.001), recurrence (P=0.011), and death due to RCC (P=0.031). PD-L1 positivity in TIICs was associated with higher nucleolar grade (P<0.001), higher T-stage (P=0.031), higher N-stage (P=0.01), recurrence (P=0.007), and death due to RCC (P=0.001). A significant positive association of time to cancer-specific death with both PD-L1-positive tumor cells and TIICs were also found. The data indicate that RCC patients with PD-L1-positive tumor cells and TIICs are at significant risk for cancer progression and the expression may be used as a complementary prognostic factor in the management of RCC patients.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2019
National Category
Urology and Nephrology Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-74192 (URN)10.1097/PAI.0000000000000766 (DOI)31058656 (PubMedID)
Available from: 2019-05-13 Created: 2019-05-13 Last updated: 2019-05-13Bibliographically approved
Carlsson, J., Christiansen, J., Davidsson, S., Giunchi, F., Fiorentino, M. & Sundqvist, P. (2019). The potential role of miR-126, miR-21 and miR-10b as prognostic biomarkers in renal cell carcinoma. Oncology Letters, 17(5), 4566-4574
Open this publication in new window or tab >>The potential role of miR-126, miR-21 and miR-10b as prognostic biomarkers in renal cell carcinoma
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2019 (English)In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 17, no 5, p. 4566-4574Article in journal (Refereed) Published
Abstract [en]

Renal cell carcinoma (RCC) is the most commonly diagnosed renal tumor, consisting of ~3% of all malignancies worldwide. The prognosis of RCC can vary widely, and detecting patients at risk of recurrence at an early stage of disease may improve patient outcome. The factors presently used in a clinical setting cannot reliably predict the natural history of the disease. Therefore, there is a requirement to identify novel biomarkers that can aid in predicting patient outcome. Previous studies have indicated that microRNAs (miRNAs/miRs) are potential candidates as prognostic biomarkers for patients suffering from RCC. Consequently, the aims of the present study were to validate the potential of 3 of these miRNAs to predict the prognosis of patients with RCC, and to investigate the stability of endogenous control genes for miRNA studies in RCC tissues. The expression of 7 endogenous controls was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in formalin-fixed paraffin-embedded tumor and benign tissues from patients suffering from clear cell RCC (ccRCC). The analyses identified RNU48 and U47 as the most stable endogenous controls. The expression of miR-126, miR-21 and miR-10b was analyzed using RT-qPCR in renal tissues from 116 patients diagnosed with ccRCC. All three investigated miRNAs were differentially expressed between malignant and benign tissues. miR-126 and miR-10b were also differentially expressed between grades and stages of ccRCC. In a univariate, but not in a multivariate model, low expression of miR-126 was associated with shorter time to recurrence of the disease. The results of the present study indicate that of the 3 miRNAs investigated, the expression of miR-126 has the strongest potential as a prognostic biomarker for patients suffering from ccRCC.

Place, publisher, year, edition, pages
Spandidos Publications, 2019
Keywords
Clear cell renal cell carcinoma, endogenous control, kidney cancer, miRNAs, renal cancer
National Category
Urology and Nephrology Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-74204 (URN)10.3892/ol.2019.10142 (DOI)000465880900065 ()30988818 (PubMedID)2-s2.0-85065252595 (Scopus ID)
Note

Funding Agency:

Örebro county research council  OLL-430521

Available from: 2019-05-10 Created: 2019-05-10 Last updated: 2019-07-23Bibliographically approved
Offermann, A., Roth, D., Hupe, M. C., Hohensteiner, S., Becker, F., Joerg, V., . . . Perner, S. (2019). TRIM24 as an independent prognostic biomarker for prostate cancer. Urologic Oncology, 37(9), Article ID 576.e1.
Open this publication in new window or tab >>TRIM24 as an independent prognostic biomarker for prostate cancer
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2019 (English)In: Urologic Oncology, ISSN 1078-1439, E-ISSN 1873-2496, Vol. 37, no 9, article id 576.e1Article in journal (Refereed) Published
Abstract [en]

Introduction: Simply applicable biomarkers for prostate cancer patients predicting the clinical course are urgently needed. Recently, TRIM24 has been identified to promote androgen receptor signaling and to correlate with an aggressive prostate cancer phenotype. Based on these data, we proofed TRIM24 as a prognostic biomarker for risk stratification.

Materials and Methods: We performed TRIM24 immunohistochemistry on 2 independent cohorts including a total of 806 primary tumors, 26 locally advanced/recurrent tumors, 30 lymph node metastases, 30 distant metastases, and 129 benign prostatic samples from 497 patients as well as on 246 prostate needle biopsies. Expression data were correlated with clinic-pathological data including biochemical recurrence-free survival (bRFS) as endpoint.

Results: Benign samples show no or low TRIM24 expression in 94%, while tumor tissues demonstrate significant higher levels. Strongest expression is observed in advanced and metastatic tumors. In multivariate analyses, TRIM24 up-regulation on radical prostatectomy specimens correlates with shorter bRFS independent of other prognostic parameters. 5-(10-) year bRFS rates for TRIM24 negative, low, medium and high expressing tumors are 93.1(93.1)%, 75.4(68.5)%, 54.9(47.5)% and 43.1(32.3)%, respectively. Of interest, tumors diagnosed as indolent disease, TRIM24 expression stratifies patients into specific risk groups. Increased TRIM24 expression associates with higher grade group, positive nodal status and extraprostatic tumor growth. TRIM24 assessment on prostate needle biopsies taken prior to treatment decision at time of initial diagnosis significantly correlates with recurrence after surgery.

Conclusion: Using 2 large independent radical prostatectomy specimen cohorts, we found that TRIM24 expression predicts patients' risk to develop disease recurrence with high accuracy and independent from other established biomarkers. Further, this is the first study exploring TRIM24 expression on prostate needle biopsies which represents the clinically relevant tissue type on which biomarkers guide treatment decisions. Thus, we strongly suggest introducing TRIM24 evaluation in prostate needle biopsies in clinical routine as an inexpensive and simple immunohistochemical test.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Prostate cancer, TRIM24, Biomarker, Disease recurrence, Immunohistochemical test
National Category
Urology and Nephrology Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-76050 (URN)10.1016/j.urolonc.2019.05.006 (DOI)000481583800016 ()31178279 (PubMedID)2-s2.0-85066785386 (Scopus ID)
Note

Funding Agencies:

German Research Foundation  DFG PE1179/9-1  PE1179/11-1 

University of Luebeck 

Available from: 2019-09-05 Created: 2019-09-05 Last updated: 2019-09-05Bibliographically approved
Ugge, H., Udumyan, R., Carlsson, J., Andrén, O., Montgomery, S., Davidsson, S. & Fall, K. (2018). Acne in late adolescence and risk of prostate cancer. International Journal of Cancer, 1580-1585
Open this publication in new window or tab >>Acne in late adolescence and risk of prostate cancer
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2018 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, p. 1580-1585Article in journal (Refereed) Published
Abstract [en]

Accumulating evidence suggest that Propionibacterium acnes may play a role in prostate carcinogenesis, but data are so far limited and inconclusive. The aim of this population-based cohort study was therefore to test whether presence of acne vulgaris during late adolescence is associated with an increased risk of prostate cancer later in life. We identified a large cohort of young men born in Sweden between 1952 and 1956, who underwent mandatory assessment for military conscription around the age of 18 (n= 243,187). Test information along with health data including medical diagnoses at time of conscription was available through the Swedish Military Conscription Register and the National Patient Register. The cohort was followed through linkages to the Swedish Cancer Register to identify the occurrence of prostate cancer until December 31st 2009. We used Cox regression to calculate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between acne in adolescence and prostate cancer risk. A total of 1,633 men were diagnosed with prostate cancer during a median follow-up of 36.7 years. A diagnosis of acne was associated with a statistically significant increased risk for prostate cancer (adjusted HR: 1.43 95%; CI: 1.06-1.92), particularly for advanced stage disease (HR: 2.37 95%; CI 1.19-4.73). A diagnosis of acne classified as severe conferred a 6-fold increased risk of prostate cancer (HR: 5.70 95% CI 1.42-22.85). Data from this large prospective population-based cohort add new evidence supporting a role of P acnes infection in prostate cancer.

Place, publisher, year, edition, pages
Hoboken, NJ, USA: John Wiley & Sons, 2018
Keywords
Propionibacterium acnes; prostate cancer; acne vulgaris; inflammation; acne vulgaris
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-63302 (URN)10.1002/ijc.31192 (DOI)000425184800009 ()29205339 (PubMedID)2-s2.0-85037982996 (Scopus ID)
Note

Funding Agency:

UK Economic and Social Research Council (ESRC)  RES-596-28-0001  ES/JO19119/1

Available from: 2017-12-11 Created: 2017-12-11 Last updated: 2019-04-09Bibliographically approved
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