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Stress-Related Signaling Pathways in Lethal and Nonlethal Prostate Cancer.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2016 Feb 01; Vol. 22 (3), pp. 765-772. Date of Electronic Publication: 2015 Oct 21. - Publication Year :
- 2016
-
Abstract
- 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.<br />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.<br />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.<br />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.<br /> (©2015 American Association for Cancer Research.)
- Subjects :
- Aged
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Glucocorticoids metabolism
Humans
Male
Middle Aged
Neoplasm Grading
Neoplasm Staging
Neovascularization, Pathologic genetics
Neovascularization, Pathologic metabolism
Prostatic Neoplasms genetics
Prostatic Neoplasms pathology
Serotonin metabolism
Biomarkers, Tumor
Prostatic Neoplasms metabolism
Signal Transduction
Stress, Physiological genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 22
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 26490316
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-15-0101