title: Depressive symptoms and cortisol rhythmicity predict survival in patients with renal cell carcinoma: role of inflammatory signaling.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of General Oncology and the Integrative Medicine Program, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America. lcohen@mdanderson.org
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cohen
authors.forename: Steven W
authors.initials: SW
authors.lastname: Cole
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.forename: Sarah
authors.initials: S
authors.lastname: Prinsloo
authors.forename: Clemens
authors.initials: C
authors.lastname: Kirschbaum
authors.forename: Jesusa M G
authors.initials: JM
authors.lastname: Arevalo
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Jennings
authors.forename: Shellie
authors.initials: S
authors.lastname: Scott
authors.forename: Luis
authors.initials: L
authors.lastname: Vence
authors.forename: Qi
authors.initials: Q
authors.lastname: Wei
authors.forename: Diane
authors.initials: D
authors.lastname: Kentor
authors.forename: Laszlo
authors.initials: L
authors.lastname: Radvanyi
authors.forename: Nizar
authors.initials: N
authors.lastname: Tannir
authors.forename: Eric
authors.initials: E
authors.lastname: Jonasch
authors.forename: Pheroze
authors.initials: P
authors.lastname: Tamboli
authors.forename: Louis
authors.initials: L
authors.lastname: Pisters
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000401:mortality / Q000523:psychology; D003863:Depression / Q000378:metabolism / Q000401:mortality / Q000523:psychology; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007249:Inflammation; D007680:Kidney Neoplasms; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction; D015996:Survival Rate; D014158:Transcription, Genetic
chemical_list: D006854:Hydrocortisone