title: Prognostic implication of serum vascular endothelial growth factor in advanced hepatocellular carcinoma staging.
abstract: BACKGROUND
  Staging systems have considerable impact on hepatocellular carcinoma (HCC) treatment approaches and outcomes. There is an unmet need to improve their stratification ability. We have evaluated four commonly used staging systems and assessed whether angiogenic biomarker vascular endothelial growth factor (VEGF) could improve their prognostic stratification.
  
  
  METHODS
  Four staging systems; Okuda, Cancer of the Liver Italian Program (CLIP), Barcelona Clinic Liver Cancer (BCLC), and Child-Pugh were evaluated in 78 HCC patients; their stratification abilities were detected by Kaplan-Meier curves and log-rank test; their accuracies of predicting survival were compared with the concordance index. Serum VEGF levels were measured using ELISA method. Recursive partitioning was used to determine the optimal VEGF cutoff. The prognostic significance of VEGF cutoff and other parameters were analyzed using univariate and multivariate models.
  
  
  RESULTS
  None of the staging systems demonstrated better discriminatory ability in predicting survival. The four staging systems did not reveal significant differences in probability of survival across their intermediate-advanced stages. Optimal cutoff identified for VEGF was 445 pg/mL. In advanced HCC, VEGF level (p = 0.004) and in early HCC, bilirubin level (p = 0.009) were identified as the independent prognostic factors. Survival comparison with high and low VEGF levels was significant for advanced HCC, while insignificant for early disease.
  
  
  CONCLUSIONS
  Staging systems with conventional parameters did not provide good prognostic stratification for survival in advanced HCC population. Serum VEGF level was an independent predictor of survival in advanced HCC, and provided more survival homogeneity within the advanced stages of conventional staging systems.
authors.affiliation: Department of Gastroenterology, Marmara University, Faculty of Medicine, lstanbul, Turkey.
authors.forename: Ender G
authors.initials: EG
authors.lastname: Yegin
authors.forename: Aydos
authors.initials: A
authors.lastname: Siykhymbayev
authors.forename: Fatih
authors.initials: F
authors.lastname: Eren
authors.forename: Nural
authors.initials: N
authors.lastname: Bekiroglu
authors.forename: Osman Cavit
authors.initials: OC
authors.lastname: Ozdogan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging / Q000379:methods*; D011237:Predictive Value of Tests; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A