title: Elevated IL-8, TNF-α, and MCP-1 in men with metastatic prostate cancer starting androgen-deprivation therapy (ADT) are associated with shorter time to castration-resistance and overall survival.
abstract: BACKGROUND
  Chemokines and cytokines have been implicated in progression to castration-resistant prostate cancer (CRPC).
  
  
  METHODS
  Retrospective data were accessed from 122 men with serum samples drawn at a median of 0.5 months after starting ADT for metastatic prostate cancer. MCP-1, IL-1-β, IL-2, IL-8, IL-6, and TNF-α levels were measured by multiplex electrochemiluminescence assays. A multivariable Cox model assessed the association of time to CRPC and overall survival by the protein levels and adjusted for clinical variables (age and prostate specific antigen (PSA) levels at start of ADT, race, ECOG status, and extent of metastases). Associations were reported as hazard ratio (HR) with 95% confidence interval (CI).
  
  
  RESULTS
  Median follow-up and overall survival were 44 and 42.2 months, respectively. ECOG performance status (≥1 vs. 0) was negatively associated with overall survival [HR = 2.8 (1.1-7.0), P = 0.03], and PSA nadir < 0.2 was predictive of longer time to development of CRPC [HR = 0.3 (0.2-0.5), P < 0.0001]. The HR for time to CRPC by protein above the median was 1.4 (95% CI: 0.9, 2.2, P = 0.13) for IL-8; 1.3 (95% CI: 0.8, 2, P = 0.18) for TNF-α; 1.0 (95% CI: 0.7, 1.6, P = 0.95) for MCP-1. The HR for median overall survival for protein levels above the median was: 1.9 (95% CI: 1.0, 3.5, P = 0.04) for IL-8; 2.0 (95% CI: 1.1, 3.5, P = 0.02) for TNF-α; 1.7 (95% CI: 1.7, 3.0, P = 0.08) for MCP-1. There was no association with IL-1-β, IL-2, or IL-6.
  
  
  CONCLUSIONS
  Higher levels of inflammation-associated cytokines correlate with poorer prostate cancer outcomes and may guide strategies to improve prostate cancer therapy.
authors.affiliation: Department of Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Jaya
authors.initials: J
authors.lastname: Sharma
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Gray
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Harshman
authors.forename: Carolyn
authors.initials: C
authors.lastname: Evan
authors.forename: Mari
authors.initials: M
authors.lastname: Nakabayashi
authors.forename: Raina
authors.initials: R
authors.lastname: Fichorova
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rider
authors.forename: Lorelei
authors.initials: L
authors.lastname: Mucci
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sweeney
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000097:blood; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000097:blood; D015331:Cohort Studies; D005500:Follow-Up Studies; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000097:blood; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000097:blood; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000726:Androgen Antagonists; D014408:Biomarkers, Tumor; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha
keywords: TNF-α and MCP-1; elevated IL-8; inflammation; prostate cancer