Affiliation:
1. 2nd Department of Pediatrics, Semmelweis University, H-1094 Budapest, Hungary
2. MTA TTK Lendület Cancer Biomarker Research Group, Institute of Enzymology, Hungarian Academy of Sciences, Magyar tudósok körútja 2, H-1117 Budapest, Hungary
Abstract
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.
Funder
Nemzeti Kutatási, Fejlesztési és Innovációs Hivatal
Cited by
297 articles.
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