Background: Potential prognostic biomarker candidates for hepatocellular carcinoma
(HCC) are abundant, but their generalizability is unexplored. We cross-validated markers
of overall survival (OS) and vascular invasion in independent datasets. Methods: The
literature search yielded 318 genes related to survival and 52 related to vascular
invasion. Validation was performed in three datasets (RNA-seq, n = 371; Affymetrix
arrays, n = 91; Illumina gene chips, n = 135) by uni-and multivariate Cox regression
and Mann-Whitney U-test, separately for Asian and Caucasian patients. Results: One
hundred and eighty biomarkers remained significant in Asian and 128 in Caucasian subjects
at p <0.05. After multiple testing correction BIRC5 (p =1.9 x 10(-10)), CDC20 (p =
2.5 x 10(-9)) and PLK1 (p = 3 x 10(-9)) endured as best performing genes in Asian
patients; however, none remained significant in the Caucasian cohort. In a multivariate
analysis, significance was reached by stage (p = 0.0018) and expression of CENPH (p
= 0.0038) and CDK4 (p = 0.038). KIF18A was the only gene predicting vascular invasion
in the Affymetrix and Illumina cohorts ( p = 0.003 and p = 0.025, respectively). Conclusion:
Overall, about half of biomarker candidates failed to retain prognostic value and
none were better than stage predicting OS. Impact: Our results help to eliminate biomarkers
with limited capability to predict OS and/or vascular invasion.
