title: Clinical and prognostic implications of plasma insulin-like growth factor-1 and vascular endothelial growth factor in patients with hepatocellular carcinoma.
abstract: OBJECTIVE
  Cirrhosis and hepatocellular carcinoma (HCC) together form a two-disease state that affects survival of patients with HCC and dictates treatment decisions and prognostic stratification of patients in clinical trials. The study objective was to improve prognostic stratification of patients with HCC.
  
  
  METHODS
  We prospectively collected plasma samples and baseline clinicopathologic features from 288 new patients with HCC, and plasma insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) levels were tested. We applied Cox regression and log-rank tests to assess association of IGF-1 and VEGF with overall survival (OS), Kaplan-Meier curves to estimate OS, and recursive partitioning to determine optimal cutoff points for IGF-1 and VEGF. Prognostic ability of conventional and molecular Barcelona Clinic Liver Cancer classifications was compared using the c-index.
  
  
  RESULTS
  Lower plasma IGF-1 and higher plasma VEGF levels significantly correlated with advanced clinicopathologic parameters and poor OS, with optimal cut points of 26 ng/mL and 450 pg/mL, respectively. The combination of low IGF-1 and high VEGF predicted median OS of 2.7 months compared with 19 months for patients with high IGF-1 and low VEGF (P < .001), further refining the prognostic ability of conventional HCC staging (P < .001).
  
  
  CONCLUSIONS
  Baseline levels of plasma IGF-1 and VEGF correlated significantly with survival in patients with HCC. Integrating IGF-1 and VEGF into HCC staging significantly enhanced prognostic stratification of patients. If validated, these results may prove to be useful in designing strategies to personalize management approaches among these patients.
authors.affiliation: Department of Gastrointestinal Medical Oncology, Unit 426, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. akaseb@mdanderson.org
authors.forename: Ahmed O
authors.initials: AO
authors.lastname: Kaseb
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Morris
authors.forename: Manal M
authors.initials: MM
authors.lastname: Hassan
authors.forename: Adnan M
authors.initials: AM
authors.lastname: Siddiqui
authors.forename: E
authors.initials: E
authors.lastname: Lin
authors.forename: Lianchun
authors.initials: L
authors.lastname: Xiao
authors.forename: Eddie K
authors.initials: EK
authors.lastname: Abdalla
authors.forename: Jean-Nicolas
authors.initials: JN
authors.lastname: Vauthey
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Aloia
authors.forename: Sunil
authors.initials: S
authors.lastname: Krishnan
authors.forename: James L
authors.initials: JL
authors.lastname: Abbruzzese
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000473:pathology; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008113:Liver Neoplasms / Q000097:blood* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I