title: Serum insulin-like growth factor-I level is an independent predictor of recurrence and survival in early hepatocellular carcinoma: a prospective cohort study.
abstract: OBJECTIVE
  Insulin-like growth factor-I (IGF-I) reflects hepatic synthetic function and plays an important role in the development and progression of various cancers. In this study, we investigated whether pretreatment serum IGF-I levels predict time-to-recurrence (TTR) and overall survival (OS) in patients with early-stage hepatocellular carcinoma after curative treatment.
  
  
  METHODS
  Consecutive patients with hepatocellular carcinoma who had undergone surgical resection, radiofrequency ablation, or percutaneous ethanol injection as curative treatments of early hepatocellular carcinoma were included from two prospective cohorts and the training set (n = 101) and the validation set (n = 91) were established. Serum samples were collected before treatment and the levels of IGF-I and IGF-binding protein-3 (IGFBP-3) were analyzed with regard to their associations with recurrence and survival.
  
  
  RESULTS
  In the training set, patients with low IGF-I levels showed significantly shorter TTR [median, 14.6 months; 95% confidence interval (CI), 1.8-27.5] than patients with high IGF-I levels (median, 50.8 months; 95% CI, 36.9-64.7; P < 0.001) during a median follow-up period of 52.4 months. In the multivariate analysis, low levels of IGF-I were an independent predictor of recurrence (HR, 2.49; 95% CI, 1.52-4.08; P < 0.001). Furthermore, together with high-serum α-fetoprotein and multiple tumors, low levels of IGF-I remained an independent predictor of poorer survival (HR, 8.00; 95% CI, 1.94-33.01; P = 0.004). Applied to the independent validation set, low-serum IGF-I levels maintained their prognostic value for shorter TTR and OS.
  
  
  CONCLUSIONS
  Low-baseline IGF-I levels independently correlated with shorter TTR and poorer survival in patients with early-stage hepatocellular carcinoma after curative treatment.
authors.affiliation: Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Cho
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Jeong-Ju
authors.initials: JJ
authors.lastname: Yoo
authors.forename: Won-Mook
authors.initials: WM
authors.lastname: Choi
authors.forename: Min Jong
authors.initials: MJ
authors.lastname: Lee
authors.forename: Yuri
authors.initials: Y
authors.lastname: Cho
authors.forename: Dong Hyeon
authors.initials: DH
authors.lastname: Lee
authors.forename: Yun Bin
authors.initials: YB
authors.lastname: Lee
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Kwon
authors.forename: Su Jong
authors.initials: SJ
authors.lastname: Yu
authors.forename: Jeong Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Kyung-Suk
authors.initials: KS
authors.lastname: Suh
authors.forename: Kion
authors.initials: K
authors.lastname: Kim
authors.forename: Yoon Jun
authors.initials: YJ
authors.lastname: Kim
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Yoon
authors.forename: Chung Yong
authors.initials: CY
authors.lastname: Kim
authors.forename: Hyo-Suk
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000235:genetics / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008113:Liver Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D044967:Serum / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I