A telomere-based prognostic model incorporating E2F1, MYCN, VPS72, CFAP53, OR8A1, and TXNRD1 for hepatocellular carcinoma

Eur J Med Res. 2026 Jan 20;31(1):293. doi: 10.1186/s40001-026-03900-4.

Abstract

Background: Hepatocellular carcinoma (HCC) is an aggressive malignancy associated with an unfavorable prognosis. Telomeres and telomere-related genes are central to tumorigenesis, but their systematic integration into prognostic modeling for HCC remains insufficiently explored. This study presents a telomere-based prognostic model aimed at improving risk stratification and informing therapeutic decision-making in HCC.

Methods: Transcriptomic profiles and clinical data were collected from The Cancer Genome Atlas (369 HCC and 50 normal samples) and Hepatocellular Carcinoma Gene Expression Database (203 cases). A curated panel of 2,093 telomere-related genes was retrieved from TelNet. Hub genes were identified using an integrated strategy combining ssGSEA, WGCNA, and differential expression analysis. A prognostic risk model was established using univariate Cox, LASSO, and multivariate Cox regression analyses, followed by external validation.

Results: We developed a robust telomere-based prognostic model featuring six key genes: E2F1, MYCN, VPS72, CFAP53, OR8A1, and TXNRD1. This six-gene signature stratified patients with HCC into high- and low-risk subgroups with significantly different overall survival (P < 0.05) across training and validation cohorts. Multivariate analyses confirmed the risk score as an independent prognostic factor. Functional analysis revealed significant enrichment of DNA replication and cell cycle pathways in high-risk patients. Immune profiling showed distinct infiltration patterns and elevated immune evasion potential in the high-risk group. Drug sensitivity analyses highlighted potential therapeutic vulnerabilities to specific inhibitors.

Conclusion: This study established a telomere-based prognostic model for HCC. This model provides reliable survival prediction, captures key tumor microenvironment features, and yields insights to support personalized therapeutic strategies, offering a valuable tool for clinical decision-making in HCC.

Keywords: Biomarker; Hepatocellular carcinoma; Immune microenvironment; Personalized therapy; Prognostic model; Telomere-related gene.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / mortality
  • Carcinoma, Hepatocellular* / pathology
  • E2F1 Transcription Factor / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / mortality
  • Liver Neoplasms* / pathology
  • Male
  • Middle Aged
  • N-Myc Proto-Oncogene Protein / genetics
  • Prognosis
  • Telomere* / genetics
  • Vesicular Transport Proteins / genetics

Substances

  • E2F1 Transcription Factor
  • E2F1 protein, human
  • N-Myc Proto-Oncogene Protein
  • MYCN protein, human
  • Biomarkers, Tumor
  • Vesicular Transport Proteins