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 non-lethal disease.
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.
Differential mRNA expression of genes within the adrenergic (p=0. 001), glucocorticoid (p
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.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2015 Oct 21 [Epub ahead of print]
Donghao Lu, Jennifer A Sinnott, Unnur A Valdimarsdottir, Fang Fang, Travis Gerke, Svitlana Tyekucheva, Michelangelo Fiorentino, Mats Lambe, Howard D Sesso, Christopher J Sweeney, Kathryn M Wilson, Edward L Giovannucci, Massimo Loda, Lorelei A Mucci, Katja Fall
Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Department of Statistics, Ohio State University. , Centre of Public Health Sciences, University of Iceland. , Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. , Department of Epidemiology, Harvard School of Public Health. , Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute. , Pathology Unit, Addarii Institute, S Orsola-Malpighi Hospital. , Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. , Brigham and Women's Hospital, Harvard School of Public Health. , Medical Oncology, Dana-Farber Cancer Institute. , Department of Epidemiology, Harvard School of Public Health. , Department of Nutrition & Epidemiology, Harvard School of Public Health. , Department of Medical Oncology, Dana-Farber Cancer Institute. , Medicine, Brigham and Women's Hospital, and Harvard Medical School. , Clinical Epidemiology Unit, Örebro University Hospital and Örebro University.