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Cited by 507Hepatocellular Carcinoma Treatment and PrognosisGene expression and cancer classificationBreast Cancer Treatment Studies

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

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Menyhárt, Otília, Nagy, Ádám, Győrffy, Balázs·2018·Royal Society Open Science
DOI 10.1098/rsos.181006PMC PMC6304123
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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.

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  • In patients with HCC, high PROX1 expression is associated with increased survival.

    “in patients with HCC, high PROX1 expression or chromosomal amplifications including PROX1 were both associated with increased survival25–32”

    From Active repression of cell fate plasticity by PROX1 safeguards hepatocyte identity and prevents liver tumorigenesis (2025) · cites this paper as [32]

    The Results section on prognostic biomarker candidates reports that high expression of some genes was associated with improved survival, but the passages found do not identify PROX1 among them. Searches for PROX1 and for PROX1 expression or amplification in relation to survival found no passage addressing the claimed association. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

  • In patients with HCC, chromosomal amplifications including PROX1 are associated with increased survival.

    “in patients with HCC, high PROX1 expression or chromosomal amplifications including PROX1 were both associated with increased survival25–32”

    From Active repression of cell fate plasticity by PROX1 safeguards hepatocyte identity and prevents liver tumorigenesis (2025) · cites this paper as [32]

    The Results section reports HCC survival associations for other genes, but the passages retrieved by searching for PROX1 and chromosomal amplification do not identify a PROX1 amplification–survival association. The Discussion mentions copy-number gains of E2F1, not PROX1; our copy therefore does not address the specific claim. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Menyhárt, O., Nagy, Á., & Győrffy, B.
Affiliations
Semmelweis University (HU)
Corresponding author
Győrffy, Balázs
ORCID
Venue
Royal Society Open Science
Publisher
The Royal Society
Published
2018-12
Volume
5
Issue
12
Pages
181006
ISSN
2054-5703 (ISSN-L)
DOI
10.1098/rsos.181006
PMC
PMC6304123
OpenAlex
W2902488470
Cited by
507
References
3
Citations by year
2026: 22 · 2025: 44 · 2024: 58 · 2023: 52 · 2022: 89 · 2021: 140 · 2020: 76 · 2019: 26
FWCI
38.07
Type
journal article
Language
en
Open access
Licence
Locations
  • Royal Society Open Science (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Nemzeti Kutatási, Fejlesztési és Innovációs Hivatal (FIEK_16-1-2016-0005, KH-129581, NVKP_16-1-2016-0037)
Topics
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
Keywords
hepatocellular carcinoma, prognostic factors, overall survival, vascular invasion, gene expression signatures, survivin, CDC20, PLK1, CDK4, KIF18A, tumor stage

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