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Cited by 197Cancer, Stress, Anesthesia, and Immune ResponseStress Responses and CortisolRenal cell carcinoma treatment

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Depressive Symptoms and Cortisol Rhythmicity Predict Survival in Patients with Renal Cell Carcinoma: Role of Inflammatory Signaling

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Cohen, Lorenzo, Cole, Steven W., Sood, Anil K., Prinsloo, Sarah, Kirschbaum, Clemens, Arevalo, Jesusa M. G., Jennings, Nicholas B., Scott, Shellie, Vence, Luis, Wei, Qi, Kentor, Diane, Radvanyi, Laszlo, Tannir, Nizar, Jonasch, Eric, Tamboli, Pheroze, Pisters, Louis·2012·PLoS ONE
DOI 10.1371/journal.pone.0042324PMC PMC3409855
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Abstract

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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Figure 1 This figure shows proportional survival curves adjusted for risk category. CES-D scores were categorized as greater or equal to 16 or less than 16 (p = 0.05, HR = 1.5, 95% CI for HR: 1.0–2.2). Survival function of 1 SD above and below the raw means was estimated for cortisol slope (p = 0.002; HR = 1.9; 95%CI for HR: 1.3–3.0).
Figure 1 This figure shows proportional survival curves adjusted for risk category. CES-D scores were categorized as greater or equal to 16 or less than 16 (p = 0.05, HR = 1.5, 95% CI for HR: 1.0–2.2). Survival function of 1 SD above and below the raw means was estimated for cortisol slope (p = 0.002; HR = 1.9; 95%CI for HR: 1.3–3.0).CC BY · PubMed Central
Figure 2 This figure shows differential leukocyte gene expressions in patients scoring greater or equal to 16 versus less than 16 on the CES-D.
Figure 2 This figure shows differential leukocyte gene expressions in patients scoring greater or equal to 16 versus less than 16 on the CES-D.CC BY · PubMed Central
Figure 3 This figure shows representative images of immunohistochemical staining for CD68, HIF1α, MMP-2, MMP-9, and COX-2 in patients scoring greater or equal to 16 versus less than 16 on the CES-D. Pictures were taken at original magnification X200.
Figure 3 This figure shows representative images of immunohistochemical staining for CD68, HIF1α, MMP-2, MMP-9, and COX-2 in patients scoring greater or equal to 16 versus less than 16 on the CES-D. Pictures were taken at original magnification X200.CC BY · PubMed Central

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  1. [46]Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, et al (2010) Development of monocytes, macrophages, and dendritic cells. Science 327: 656– 661. 20133564 PMC2887389

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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)
DOI
10.1371/journal.pone.0042324
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
Licence
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Stress, Anesthesia, and Immune Response
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Oncology › 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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