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Stress-Related Signaling Pathways in Lethal and Nonlethal Prostate Cancer
Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Statistics, Ohio State University, Columbus OH, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA.
Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Faculty of Medicine, Center of Public Health Sciences, School of Health Sciences, University of Iceland, Reykjavík, Iceland.
Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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2016 (English)In: Clinical cancer research : an official journal of the American Association for Cancer Research, ISSN 1078-0432, Vol. 22, no 3, p. 765-772Article in journal (Refereed) Published
Abstract [en]

Purpose: Recent data suggest that neuroendocrine signaling may influence progression in some cancers. We aimed to determine whether genes within the five major stress-related signaling pathways are differentially expressed in tumor tissue when comparing prostate cancer patients with lethal and nonlethal disease.

Experimental design: We measured mRNA expression of 51 selected genes involved in predetermined stress-related signaling pathways (adrenergic, glucocorticoid, dopaminergic, serotoninergic, and muscarinic systems) in tumor tissue and normal prostate tissue collected from prostate cancer patients in the Physicians' Health Study (n = 150; n = 82 with normal) and the Health Professionals Follow-Up Study (n = 254; n = 120 with normal). We assessed differences in pathway expression in relation to prostate cancer lethality as the primary outcome and to biomarkers as secondary outcomes.

Results: Differential mRNA expression of genes within the adrenergic (P = 0.001), glucocorticoid (P < 0.0001), serotoninergic (P = 0.0019), and muscarinic (P = 0.0045) pathways in tumor tissue was associated with the risk of lethality. The adrenergic pathway was also statistically significant (P = 0.001) when comparing against differential expression of genes not involved in the pathways. In adjacent normal prostate tissue, none of the pathways was clearly differentially expressed between lethal and nonlethal prostate cancer. The glucocorticoid and adrenergic pathways were associated with cell proliferation, while the glucocorticoid pathway was additionally associated with angiogenesis and perineural invasion.

Conclusions: Our study suggests that stress-related signaling pathways, particularly the adrenergic and glucocorticoid, may be dysregulated in the tumors of men whose prostate cancer proves to be lethal, and motivates further investigation of these pathways in functional studies.

Place, publisher, year, edition, pages
Philadelphia, USA: American Association for Cancer Research , 2016. Vol. 22, no 3, p. 765-772
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:oru:diva-47342DOI: 10.1158/1078-0432.CCR-15-0101ISI: 000369083300026PubMedID: 26490316OAI: oai:DiVA.org:oru-47342DiVA, id: diva2:891552
Funder
Swedish Cancer Society, CAN 2013/650
Note

Funding Agencies:

Partial Financing of New Doctoral Student (KID) from the Karolinska Institutet

NIH T32GM074897 T32 CA09001 CA136578 CA090381

A. David Mazzone Career Development Award

Svenska Sällskapet for Medicinsk Forskning

Strategic funding from Örebro University

Prostate Cancer Foundation CA34944

CA40360 CA097193 HL26490 HL34595 CA133891 CA141298 P01CA055075

Available from: 2016-01-07 Created: 2016-01-07 Last updated: 2018-07-09Bibliographically approved

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