Royal Society Open Science (Jan 2018)

Determining consistent prognostic biomarkers of overall survival and vascular invasion in hepatocellular carcinoma

  • Otília Menyhárt,
  • Ádám Nagy,
  • Balázs Győrffy

DOI
https://doi.org/10.1098/rsos.181006
Journal volume & issue
Vol. 5, no. 12

Abstract

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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 × 10−10), CDC20 (p = 2.5 × 10−9) and PLK1 (p = 3 × 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.

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