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

O Menyhárt, Á Nagy, B Győrffy - Royal Society open …, 2018 - royalsocietypublishing.org
Royal Society open science, 2018royalsocietypublishing.org
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 …
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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