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Andersson, Swen-Olof
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Publications (10 of 55) Show all publications
Stopsack, K. H., Gerke, T. A., Andrén, O., Andersson, S.-O., Giovannucci, E. L., Mucci, L. A. & Rider, J. R. (2017). Cholesterol uptake and regulation in high-grade and lethal prostate cancers. Carcinogenesis, 38(8), 806-811
Open this publication in new window or tab >>Cholesterol uptake and regulation in high-grade and lethal prostate cancers
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2017 (English)In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 38, no 8, p. 806-811Article in journal (Refereed) Published
Abstract [en]

Lethal prostate cancers have higher expression of squalene monooxygenase (SQLE), the second rate-limiting enzyme of cholesterol synthesis. Preclinical studies suggested that aberrant cholesterol regulators, receptors and transporters contribute to cholesterol accumulation uniformly. We assessed their association with features of aggressive cancers. In the prospective prostate cancer cohorts within the Health Professional Follow-up Study, the Physicians' Health Study and the Swedish Watchful Waiting Study, tumor mRNA expression profiling was performed. Lethal disease was defined as mortality or metastases from prostate cancer (n = 266) in contrast to non-lethal disease without metastases after >8 years of follow-up (n = 476). Associations with Gleason grade were additionally assessed using The Cancer Genome Atlas primary prostate cancer dataset (n = 333). Higher Gleason grade was associated with lower LDLR expression, lower SOAT1 and higher SQLE expression. Besides high SQLE expression, cancers that became lethal despite primary treatment were characterized by low LDLR expression (odds ratio for highest versus lowest quintile, 0.37; 95% CI 0.18-0.76) and by low SOAT1 expression (odds ratio, 0.41; 95% CI 0.21-0.83). The association of LDLR expression and lethality was not present in tumors with high IDOL expression. ABCA1, PCSK9 or SCARB1 expressions were not associated with Gleason grade or lethal cancer. In summary, prostate cancers that progress to lethal disease rely on de novo cholesterol synthesis (via SQLE), rather than transcellular uptake (via LDLR) or cholesterol esterification (via SOAT1). These results may help design pharmacotherapy for high-risk patients.

Place, publisher, year, edition, pages
Oxford University Press, 2017
National Category
Medical Genetics Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-61799 (URN)10.1093/carcin/bgx058 (DOI)000406831800006 ()28595267 (PubMedID)2-s2.0-85028413926 (Scopus ID)
Note

Funding agencies:

National Institutes of Health UM1 CA167552 

Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence program in Prostate Cancer 5P50CA090381-08 

National Cancer Institute CA141298 CA133891  CA097193  CA34944  CA40360  HL26490  HL34595 

Available from: 2017-10-23 Created: 2017-10-23 Last updated: 2018-09-17Bibliographically approved
Downer, M. K., Batista, J. L., Mucci, L. A., Stampfer, M. J., Epstein, M. M., Håkansson, N., . . . Andersson, S.-O. (2017). Dairy intake in relation to prostate cancer survival. International Journal of Cancer, 140(9), 2060-2069
Open this publication in new window or tab >>Dairy intake in relation to prostate cancer survival
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2017 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 140, no 9, p. 2060-2069Article in journal (Refereed) Published
Abstract [en]

Dairy intake has been associated with increased risk of advanced prostate cancer. Two US cohort studies reported increased prostate cancer-specific mortality with increased high-fat milk intake. We examined whether dairy and related nutrient intake were associated with prostate cancer progression in a Swedish patient population with high dairy consumption. We prospectively followed 525 men with newly diagnosed prostate cancer (diagnosed 1989-1994). We identified and confirmed deaths through February 2011 (n = 222 prostate cancer-specific, n = 268 from other causes). Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the associations between food or nutrient intake and prostate cancer-specific death. On average, patients consumed 5.0 servings/day of total dairy products at diagnosis. In the whole population, high-fat milk intake was not associated with prostate cancer-specific death (95% CI: 0.78, 2.10; p-trend = 0.32; multivariate-adjusted model). However, among patients diagnosed with localized prostate cancer, compared to men who consumed <1 servings/day of high-fat milk, those who drank >= 3 servings/day had an increased hazard of prostate cancer mortality (HR = 6.10; 95% CI: 2.14, 17.37; p-trend = 0.004; multivariate-adjusted model). Low-fat milk intake was associated with a borderline reduction in prostate cancer death among patients with localized prostate cancer. These associations were not observed among patients diagnosed with advanced stage prostate cancer. Our data suggest a positive association between high-fat milk intake and prostate cancer progression among patients diagnosed with localized prostate cancer. Further studies are warranted to investigate this association and elucidate the mechanisms by which high-fat milk intake may promote prostate cancer progression.

Place, publisher, year, edition, pages
Hoboken: John Wiley & Sons, 2017
Keywords
prostate cancer, dairy, milk, prostate cancer mortality, diet
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-57668 (URN)10.1002/ijc.30642 (DOI)000399313000013 ()28187509 (PubMedID)2-s2.0-85013387704 (Scopus ID)
Available from: 2017-05-16 Created: 2017-05-16 Last updated: 2018-07-31Bibliographically approved
Lu, D., Carlsson, J., Penney, K. L., Davidsson, S., Andersson, S.-O., Mucci, L. A., . . . Fall, K. (2017). Expression and Genetic Variation in Neuroendocrine Signaling Pathways in Lethal and Nonlethal Prostate Cancer among Men Diagnosed with Localized Disease. Cancer Epidemiology, Biomarkers and Prevention, 26(12), 1781-1787
Open this publication in new window or tab >>Expression and Genetic Variation in Neuroendocrine Signaling Pathways in Lethal and Nonlethal Prostate Cancer among Men Diagnosed with Localized Disease
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2017 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 26, no 12, p. 1781-1787Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Recent data suggest that neuroendocrine signaling pathways may play a role in the progression of prostate cancer, particularly for early-stage disease. We aimed to explore whether expression of selected genes in the adrenergic, serotoninergic, glucocorticoid, and dopaminergic pathways differs in prostate tumor tissue from men with lethal disease compared to men with nonlethal disease.

METHODS: Based on the Swedish Watchful Waiting Cohort, we included 511 men diagnosed with incidental prostate cancer through TURP during 1977-1998 with follow-up up to 30 years. For those with tumor tissue (N=262), we measured mRNA expression of 223 selected genes included in neuroendocrine pathways. Using DNA from normal prostate tissue (N=396), we genotyped 36 SNPs from 14 receptor genes. Lethal prostate cancer was the primary outcome in analyses with pathway gene expression and genetic variants.

RESULTS: Differential expression of genes in the serotoninergic pathway was associated with risk of lethal prostate cancer (P=0.007); similar but weaker associations were noted for the adrenergic (P=0.014) and glucocorticoid (P=0.020) pathways. Variants of the HTR2A (rs2296972; P=0.002) and NR3CI (rs33388; P=0.035) genes (within the serotoninergic and glucocorticoid pathways) were associated with lethal cancer in over-dominant models. These genetic variants were correlated with expression of several genes in corresponding pathways (P<0.05).

CONCLUSIONS: Our findings lend support to hypothesis that the neuroendocrine pathways, particularly serotoninergic pathway, are associated with lethal outcome in the natural course of localized prostate cancer.

IMPACT: The current study provides evidence of the role of neuroendocrine pathways in prostate cancer progression which may have clinical utility.

Place, publisher, year, edition, pages
American Association for Cancer Research, 2017
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-62461 (URN)10.1158/1055-9965.EPI-17-0453 (DOI)000416858600012 ()28939587 (PubMedID)2-s2.0-85036617593 (Scopus ID)
Funder
Swedish Cancer Society, CAN 2013/650 CAN 2014/417
Note

Funding Agencies:

Karolinska Institutet and Robert Lundberg's Foundation  2016lund47503 

Karolinska Institutet 

Örebro University

Available from: 2017-12-04 Created: 2017-12-04 Last updated: 2018-09-06Bibliographically approved
Zareba, P., Flavin, R., Isikbay, M., Rider, J. R., Gerke, T. A., Finn, S., . . . Mucci, L. A. (2017). Perineural Invasion and Risk of Lethal Prostate Cancer. Cancer Epidemiology, Biomarkers and Prevention, 26(5), 719-726
Open this publication in new window or tab >>Perineural Invasion and Risk of Lethal Prostate Cancer
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2017 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 26, no 5, p. 719-726Article in journal (Refereed) Published
Abstract [en]

Background: Prostate cancer has a propensity to invade and grow along nerves, a phenomenon called perineural invasion (PNI). Recent studies suggest that the presence of PNI in prostate cancer has been associated with cancer aggressiveness.

Methods: We investigated the association between PNI and lethal prostate cancer in untreated and treated prostate cancer cohorts: the Swedish Watchful Waiting Cohort of 615 men who underwent watchful waiting, and the U.S. Health Professionals Follow-Up Study of 849 men treated with radical prostatectomy. One pathologist performed a standardized histopathologic review assessing PNI and Gleason grade. Patients were followed from diagnosis until metastasis or death.

Results: The prevalence ofPNI was7% and 44% in the untreated and treated cohorts, respectively. PNI was more common in high Gleason grade tumors in both cohorts. PNI was associated with enhanced tumor angiogenesis, but not tumor proliferation or apoptosis. In the Swedish study, PNI was associated with lethal prostate cancer [OR 7.4; 95% confidence interval (CI), 3.6-16.6; P < 0.001]. A positive, although not statistically significant, associationpersisted after adjustment for age, Gleason grade, and tumor volume (OR 1.9; 95% CI, 0.8-5.1; P = 0.17). In the U.S. study, PNI predicted lethal prostate cancer independent of clinical factors (HR 1.8; 95% CI, 1.0, 3.3; P = 0.04).

Conclusions: These data support the hypothesis that perineural invasion creates a microenvironment that promotes cancer aggressiveness. Impact: Our findings suggest that PNI should be a standardized component of histopathologic review, and highlights a mechanism underlying prostate cancer metastasis. (C) 2017 AACR.

Place, publisher, year, edition, pages
American Association for Cancer Research Inc., 2017
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-57864 (URN)10.1158/1055-9965.EPI-16-0237 (DOI)000400524700008 ()28062398 (PubMedID)2-s2.0-85015798340 (Scopus ID)
Funder
Swedish Cancer Society, CAN 2006/1341Swedish Research Council, 2009-7309
Note

Funding Agencies:

NIH  PO1 CA055075  CA141298  CA13389  UM1 CA167552 

U.S. Army Prostate Cancer Research Program Idea Development Award  PC060389 

DF/HCC Prostate SPORE Career Development Award  NIH/NCI P50 CA90381 

Prostate Cancer Foundation Young Investigator Awards

Royal Physiographic Society in Lund, Sweden

Available from: 2017-05-31 Created: 2017-05-31 Last updated: 2018-07-31Bibliographically approved
Stopsack, K. H., Gerke, T. A., Sinnott, J. A., Penney, K. L., Tyekucheva, S., Sesso, H. D., . . . Rider, J. R. (2016). Cholesterol Metabolism and Prostate Cancer Lethality. Cancer Research, 76(16), 4785-4790
Open this publication in new window or tab >>Cholesterol Metabolism and Prostate Cancer Lethality
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2016 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 76, no 16, p. 4785-4790Article in journal (Refereed) Published
Abstract [en]

Cholesterol metabolism has been implicated in prostate cancer pathogenesis. Here, we assessed the association of intratumoral mRNA expression of cholesterol synthesis enzymes, transporters, and regulators in tumor specimen at diagnosis and lethal prostate cancer, defined as mortality or metastases from prostate cancer in contrast to nonlethal disease without evidence of metastases after at least 8 years of follow-up. We analyzed the prospective prostate cancer cohorts within the Health Professionals Follow-up Study (n = 249) and the Physicians' Health Study (n = 153) as well as expectantly managed patients in the Swedish Watchful Waiting Study (n = 338). The expression of squalene monooxygenase (SQLE) was associated with lethal cancer in all three cohorts. Men with high SQLE expression (>1 standard deviation above the mean) were 8.3 times (95% confidence interval, 3.5 to 19.7) more likely to have lethal cancer despite therapy compared with men with the mean level of SQLE expression. Absolute SQLE expression was associated with lethal cancer independently from Gleason grade and stage, as was a SQLE expression ratio in tumor versus surrounding benign prostate tissue. Higher SQLE expression was tightly associated with increased histologic markers of angiogenesis. Collectively, this study establishes the prognostic value of intratumoral cholesterol synthesis as measured via SQLE, its second rate-limiting enzyme. SQLE expression at cancer diagnosis is prognostic for lethal prostate cancer both after curative-intent prostatectomy and in a watchful waiting setting, possibly by facilitating micrometastatic disease.

Place, publisher, year, edition, pages
American Association for Cancer Research Inc., 2016
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-52692 (URN)10.1158/0008-5472.CAN-16-0903 (DOI)000382297700020 ()27325648 (PubMedID)2-s2.0-84982168574 (Scopus ID)
Available from: 2016-10-03 Created: 2016-09-30 Last updated: 2018-09-06Bibliographically approved
Davidsson, S., Mölling, P., Rider, J. R., Unemo, M., Karlsson, M. G., Carlsson, J., . . . Andrén, O. (2016). Erratum to: Frequency and typing of Propionibacterium acnes in prostate tissue obtained from men with and without prostate cancer. Infectious Agents and Cancer, 11, Article ID 36.
Open this publication in new window or tab >>Erratum to: Frequency and typing of Propionibacterium acnes in prostate tissue obtained from men with and without prostate cancer
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2016 (English)In: Infectious Agents and Cancer, ISSN 1750-9378, E-ISSN 1750-9378, Vol. 11, article id 36Article in journal (Refereed) Published
Place, publisher, year, edition, pages
London, United kingdom: BioMed Central, 2016
National Category
Cancer and Oncology Immunology in the medical area
Research subject
Oncology; Immunology
Identifiers
urn:nbn:se:oru:diva-51080 (URN)10.1186/s13027-016-0084-7 (DOI)000379538600001 ()27335583 (PubMedID)2-s2.0-84979031501 (Scopus ID)
Note

This corrects the article Frequency and typing of Propionibacterium acnes in prostate tissue obtained from men with and without prostate cancer DOI: 10.1186/s13027-016-0074-9.

Available from: 2016-06-29 Created: 2016-06-28 Last updated: 2018-07-16Bibliographically approved
Davidsson, S., Mölling, P., Rider, J. R., Unemo, M., Karlsson, M. G., Carlsson, J., . . . Andrén, O. (2016). Frequency and typing of Propionibacterium acnes in prostate tissue obtained from men with and without prostate cancer. Infectious Agents and Cancer, 11, Article ID 26.
Open this publication in new window or tab >>Frequency and typing of Propionibacterium acnes in prostate tissue obtained from men with and without prostate cancer
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2016 (English)In: Infectious Agents and Cancer, ISSN 1750-9378, E-ISSN 1750-9378, Vol. 11, article id 26Article in journal (Refereed) Published
Abstract [en]

Background: Prostate cancer is the most common cancer among men in Western countries but the exact pathogenic mechanism of the disease is still largely unknown. An infectious etiology and infection-induced inflammation has been suggested to play a role in prostate carcinogenesis and Propionibacterium acnes has been reported as the most prevalent microorganism in prostatic tissue. We investigated the frequency and types of P. acnes isolated from prostate tissue samples from men with prostate cancer and from control patients without the disease.

Methods: We included 100 cases and 50 controls in this study. Cases were men diagnosed with prostate cancer undergoing radical prostatectomy and controls were men undergoing surgery for bladder cancer without any histological findings of prostate cancer. Six biopsies taken from each patient's prostate gland at the time of surgery were used for cultivation and further characterization of P. acnes.

Results: The results revealed that P. acnes was more common in men with prostate carcinoma than in controls, with the bacteria cultured in 60 % of the cases vs. 26 % of the controls (p = 0.001). In multivariable analyses, men with P. acnes had a 4-fold increase in odds of a prostate cancer diagnosis after adjustment for age, calendar year of surgery and smoking status (OR: 4.46; 95 % CI: 1.93-11.26). To further support the biologic plausibility for a P. acnes infection as a contributing factor in prostate cancer development, we subsequently conducted cell-based experiments. P. acnes- isolates were co-cultured with the prostate cell line PNT1A. An increased cell proliferation and cytokine/chemokine secretion in infected cells was observed.

Conclusion: The present study provides further evidence for a role of P. acnes in prostate cancer development.

Place, publisher, year, edition, pages
London, United Kingdom: BioMed Central, 2016
Keywords
Prostate cancer, propionibacterium acnes, infection, inflammation
National Category
Cancer and Oncology Urology and Nephrology
Research subject
Oncology; Immunology
Identifiers
urn:nbn:se:oru:diva-50868 (URN)10.1186/s13027-016-0074-9 (DOI)000377521800001 ()27284286 (PubMedID)2-s2.0-84975266712 (Scopus ID)
Note

The erratum to this article has been published in Infectious Agents and Cancer 2016 11:36.

Funding Agencies:

Örebro County Council Research Committee

Foundation for Medical Research at Örebro University Hospital, Sweden

Available from: 2016-06-15 Created: 2016-06-15 Last updated: 2018-08-31Bibliographically approved
Thorgeirsson, T., Jordahl, K. M., Flavin, R., Epstein, M. M., Fiorentino, M., Andersson, S.-O., . . . Mucci, L. A. (2016). Intracellular location of BRCA2 protein expression and prostate cancer progression in the Swedish Watchful Waiting Cohort. Carcinogenesis, 37(3), 262-268
Open this publication in new window or tab >>Intracellular location of BRCA2 protein expression and prostate cancer progression in the Swedish Watchful Waiting Cohort
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2016 (English)In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 37, no 3, p. 262-268Article in journal (Refereed) Published
Abstract [en]

Prostate cancer patients with inherited BRCA2 mutations have a survival disadvantage. However, it is unknown whether progression is associated with BRCA2 protein expression in diagnostic prostate cancer tissue, among men without inherited mutations. We conducted a nested case-control study within the Swedish Watchful Waiting cohort. The case group included all 71 patients who died from prostate cancer within 5 years from diagnosis and controls were all patients (n = 165) who lived at least 7 years after diagnosis. Tissue microarrays were stained using antibodies for C- and N-terminal domains of the BRCA2 protein. Location (nuclear, cytoplasmic and membranous) and magnitude (intensity and percentage) of expression were assessed. Logistic regression models produced odds ratios (OR) and 95% confidence intervals (CI) adjusted for age, year of diagnosis and Gleason score. Positive BRCA2 staining at the cell membrane was associated with reduced risk of death within 5 years (N-terminal: OR = 0.47, 95% CI = 0.21-1.04, P = 0.06; C-terminal: OR = 0.41, 95% CI = 0.18-0.91, P = 0.03) and low Gleason scores (P = 0.006). Positive cytoplasmic C-terminal staining was associated with higher Gleason scores and increased lethality (OR = 3.61, 95% CI = 1.61-8.07, P = 0.002). BRCA2 protein expression at the cell membrane and lack of C-terminal expression in the cytoplasm were associated with a reduced risk of rapidly fatal prostate cancer. BRCA2 protein expression in prostate cancer tissue may have independent prognostic value. The potential biological significance of BRCA2 expression at the cell membrane warrants further investigation.

Place, publisher, year, edition, pages
Oxford, United Kingdom: Oxford University Press, 2016
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-49212 (URN)10.1093/carcin/bgw001 (DOI)000371696400004 ()26775038 (PubMedID)2-s2.0-84959896231 (Scopus ID)
Funder
Swedish Cancer Society
Note

Funding Agencies:

Icelandic Prostate Cancer Group Framfor

Icelandic Cancer Society

Dana Farber/Harvard Cancer Center SPORE in Prostate Cancer P50 CA090381

Available from: 2016-03-10 Created: 2016-03-10 Last updated: 2018-07-10Bibliographically approved
Martin, N. E., Gerke, T., Sinnott, J. A., Stack, E. C., Andrén, O., Andersson, S.-O., . . . Loda, M. (2015). Measuring PI3K Activation: Clinicopathologic, Immunohistochemical, and RNA Expression Analysis in Prostate Cancer. Molecular Cancer Research, 13(10), 1431-1440
Open this publication in new window or tab >>Measuring PI3K Activation: Clinicopathologic, Immunohistochemical, and RNA Expression Analysis in Prostate Cancer
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2015 (English)In: Molecular Cancer Research, ISSN 1541-7786, E-ISSN 1557-3125, Vol. 13, no 10, p. 1431-1440Article in journal (Refereed) Published
Abstract [en]

Assessing the extent of PI3K pathway activity in cancer is vital to predicting sensitivity to PI3K-targeting drugs, but the best biomarker of PI3K pathway activity in archival tumor specimens is unclear. Here, PI3K pathway activation was assessed, in clinical tissue from 1,021 men with prostate cancers, using multiple pathway nodes that include PTEN, phosphorylated AKT (pAKT), phosphorylated ribosomal protein S6 (pS6), and stathmin. Based on these markers, a 9-point score of PI3K activation was created using the combined intensity of the 4-markers and analyzed its association with proliferation (Ki67), apoptosis (TUNEL), and androgen receptor (AR) status, as well as pathologic features and cancer-specific outcomes. In addition, the PI3K activation score was compared with mRNA expression profiling data for a large subset of men. Interestingly, those tumors with higher PI3K activation scores also had higher Gleason grade (P = 0.006), increased AR (r = 0.37; P < 0.001) and Ki67 (r = 0.24; P < 0.001), and decreased TUNEL (r = -0.12; P = 0.003). Although the PI3K activation score was not associated with an increased risk of lethal outcome, a significant interaction between lethal outcome, Gleason and high PI3K score (P = 0.03) was observed. Finally, enrichment of PI3K-specific pathways was found in the mRNA expression patterns differentiating the low and high PI3K activation scores; thus, the 4-marker IHC score of PI3K pathway activity correlates with features of PI3K activation.

Place, publisher, year, edition, pages
American Association for Cancer Research, 2015
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-47170 (URN)10.1158/1541-7786.MCR-14-0569 (DOI)000365604300008 ()26124442 (PubMedID)2-s2.0-84945245876 (Scopus ID)
Note

Funding Agencies:

Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence (SPORE) in Prostate Cancer P50CA090381-08

National Cancer Institute of the NIH UM1CA167552  R01CA141298  R01CA136578  R01CA131945  P01CA89021

Prostate Cancer Foundation Young Investigator awards

Available from: 2015-12-21 Created: 2015-12-21 Last updated: 2018-09-04Bibliographically approved
Sinnott, J. A., Rider, J. R., Carlsson, J., Gerke, T., Tyekucheva, S., Penney, K. L., . . . Andrén, O. (2015). Molecular differences in transition zone and peripheral zone prostate tumors. Carcinogenesis, 36(6), 632-638
Open this publication in new window or tab >>Molecular differences in transition zone and peripheral zone prostate tumors
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2015 (English)In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 36, no 6, p. 632-638Article in journal (Refereed) Published
Abstract [en]

Prostate tumors arise primarily in the peripheral zone (PZ) of the prostate, but 20-30% arise in the transition zone (TZ). Zone of origin may have prognostic value or reflect distinct molecular subtypes; however, it can be difficult to determine in practice. Using whole-genome gene expression, we built a signature of zone using normal tissue from five individuals and found that it successfully classified nine tumors of known zone. Hypothesizing that this signature captures tumor zone of origin, we assessed its relationship with clinical factors among 369 tumors of unknown zone from radical prostatectomies (RPs) and found that tumors that molecularly resembled TZ tumors showed lower mortality (P = 0.09) that was explained by lower Gleason scores (P = 0.009). We further applied the signature to an earlier study of 88 RP and 333 transurethral resection of the prostate (TURP) tumor samples, also of unknown zone, with gene expression on ~6000 genes. We had observed previously substantial expression differences between RP and TURP specimens, and hypothesized that this might be because RPs capture primarily PZ tumors, whereas TURPs capture more TZ tumors. Our signature distinguished these two groups, with an area under the receiver operating characteristic curve of 87% (P < 0.0001). Our findings that zonal differences in normal tissue persist in tumor tissue and that these differences are associated with Gleason score and sample type suggest that subtypes potentially resulting from different etiologic pathways might arise in these zones. Zone of origin may be important to consider in prostate tumor biomarker research.

Place, publisher, year, edition, pages
Oxford, United Kingdom: Oxford University Press, 2015
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-44588 (URN)10.1093/carcin/bgv051 (DOI)000356181700004 ()25870172 (PubMedID)
Funder
NIH (National Institute of Health), CA34944 CA40360 CA097193 HL26490 HL34595 UM1 CA167552 R01 HL35464 GM074897 CA09001 CA141298 CA136578 CA090381Swedish Cancer Society, CAN 2013/650
Note

Funding Agencies:

Swedish Cancer Foundation

Örebro County Council Research Foundation

A. David Mazzone Career Development Award

Örebro University

Prostate Cancer Foundation

Available from: 2015-05-12 Created: 2015-05-11 Last updated: 2018-06-30Bibliographically approved
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