Depressive Symptoms and Cortisol Rhythmicity Predict Survival in Patients with Renal Cell Carcinoma: Role of Inflammatory Signaling
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PURPOSE: Evidence has supported the association between psychological factors and cancer biology; however, findings are equivocal on the role of psychosocial factors in cancer progression. This study generates a hypothesis of mechanistic variables by examining the clinical effects of psychosocial factors and cortisol dysregulation in patients with metastatic renal cell carcinoma (RCC) and examines associated activation of transcription control pathways. METHODS: Patients with metastatic RCC (n = 217) were prospectively enrolled in this study. Patients completed questionnaires (Centers for Epidemiologic Studies-Depression; SF-36 Health Status Survey; Duke Social Support Index; Coping Operations Preference Enquiry; organized and non-organized religious activity; and intrinsic religiosity), and provided blood and saliva samples. Cortisol levels and whole genome transcriptional profiling were assessed to identify potential alterations in circadian rhythms and genomic pathways. RESULTS: Separate Cox regression models, controlling for disease risk category, revealed that CES-D scores (p = 0.05, HR = 1.5, 95% CI for HR: 1.00-2.23) and cortisol slope (p = 0.002; HR = 1.9; 95%CI for HR: 1.27-2.97) were significantly associated with decreased survival. Only cortisol slope and risk category remained significant in the complete model. Functional genomic analyses linked depressive symptoms to increased expression of pro-inflammatory and pro-metastatic genes in circulating leukocytes. 116 transcripts were found to be upregulated by an average of 50% or more in high CES-D patients, and 57 transcripts downregulated by at least 50%. These changes were also found in the tumor in a subset of patients. CONCLUSION: These findings identify depressive symptoms as a key predictor of survival in renal cell carcinoma patients with potential links to dysregulation of cortisol and inflammatory biology.
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Elevated anxiety or depression in adults with metastatic cancer can be associated with earlier cancer-related mortality.
“and earlier cancer-related mortality [20–22]”
From A randomized controlled trial of a multi-modal palliative care intervention to promote advance care planning and psychological well-being among adults with advanced cancer: study protocol. (2022) · cites this paper as [20]
The Results (page unavailable) report that higher depressive-symptom scores were associated with shorter survival among patients with metastatic renal cell carcinoma. The paper does not establish the same association for anxiety, and its survival analysis does not distinguish cancer-related deaths from deaths due to other causes. (LLM, conf=0.84)
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- Authors
- Cohen, L., Cole, S. W., Sood, A. K., Prinsloo, S., Kirschbaum, C., Arevalo, J. M. G., Jennings, N. B., Scott, S., Vence, L., Wei, Q., Kentor, D., Radvanyi, L., Tannir, N., Jonasch, E., Tamboli, P., & Pisters, L.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Technische Universität Dresden (DE)
- University of California, Los Angeles (US)
- Corresponding author
- Cohen, Lorenzo
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-08-01
- Volume
- 7
- Issue
- 8
- Pages
- e42324
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3409855
- OpenAlex
- W2106923873
- Cited by
- 197
- References
- 50
- Citations by year
- 2026: 8 · 2025: 4 · 2024: 6 · 2023: 46 · 2022: 14 · 2021: 8 · 2020: 11 · 2019: 6 · 2018: 10 · 2017: 18 · 2016: 19 · 2015: 14 · 2014: 18 · 2013: 12 · 2012: 3
- FWCI
- 10.70
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Dana Foundation
- National Institutes of Health (CA-16 672, NCI #CA16672)
- University of Texas MD Anderson Cancer Center (#CA16672, NCI CA16672)
- National Cancer Institute (CA 109298, NCI CA 16672, CA-16672, R01CA110793, CA 110793, R01CA109298, R01CA116778, CA-116778, P30CA016672)
- National Center for Complementary and Integrative Health (K01AT008485)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Renal cell carcinoma treatment
- Keywords
- depressive symptoms, cortisol, circadian rhythm, metastatic renal cell carcinoma, survival, inflammation, pro-inflammatory genes, circulating leukocytes, tumor transcriptome, psychosocial factors, religious activities, social support, coping, tumor progression
- MeSH terms
- Aged, Carcinoma, Renal Cell, Depression, Female, Humans, Hydrocortisone, Inflammation, Kidney Neoplasms, Male, Middle Aged, Transcription, Genetic, Signal Transduction, Genome, Human, Survival Rate, Disease-Free Survival, Gene Expression Profiling
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