title: Elevated insulin-like growth factor binding protein-1 (IGFBP-1) in men with metastatic prostate cancer starting androgen deprivation therapy (ADT) is associated with shorter time to castration resistance and overall survival.
abstract: BACKGROUND
  Insulin-like growth factor (IGF) and adipokines have been implicated in prostate cancer carcinogenesis.
  
  
  METHODS
  Data from 122 men with serum samples drawn within 3 months of starting ADT for metastatic prostate cancer was accessed retrospectively. IGF-1, IGF binding protein (BP)-1, leptin, and adiponectin levels were measured by multiplex electrochemiluminescence assays. A multivariable Cox model assessed the association of time to castration resistant prostate cancer (CRPC) and overall survival by the protein levels, adjusted for clinical variables, age and prostate specific antigen (PSA) levels at start of ADT, race, ECOG status, extent of metastases and 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 [H  = 2.8 (1.1-7.0), P = 0.03], and PSA nadir <0.2 was predictive of longer time to CRPC [HR = 0.3 (0.2-0.5), P < 0.0001]. The median time to CRPC by low, middle, and top IGFBP-1 tertile distribution was 20.7, 18.1, and 12.4 months, respectively, with HR for middle versus low tertile levels 3.1 (1.7-5), P = 0.0003, and for top versus low tertile levels was 2.4 (1.3-4.2), P = 0.003. The median overall survival by low, middle and top tertile IGFBP-1 level was 48.5, 46.4, and 32.8 months, respectively, with HR for top versus low tertile 2.5 (1.2-5.1), P = 0.01. There was no association with IGF-1, adiponectin and leptin.
  
  
  CONCLUSIONS
  Elevated IGFBP-1 appears to be associated with shorter time to CRPC and lower overall survival in men with metastatic prostate cancer.
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: 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: D052242:Adiponectin / Q000097:blood; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood* / Q000401:mortality* / Q000628:therapy; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood*; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors
chemical_list: D052242:Adiponectin; D018931:Antineoplastic Agents, Hormonal; D018970:Insulin-Like Growth Factor Binding Protein 1; D020738:Leptin; D017430:Prostate-Specific Antigen
keywords: adiponectin; insulin-like growth factor; leptin; prostate cancer