Integrated genetic and epigenetic biomarker landscapes in hepatocellular carcinoma: From molecular mechanisms to translational precision oncology

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Aly D.M.; Fteah A.M.; Elrefaiy M.A.; Seddik H.E.

Journal: Gene Reports

Publisher: Elsevier Inc.

Publication Date: 2026

Volume / Issue: Volume 45

Article No.: 102597

ISSN: 24520144

DOI: 10.1016/j.genrep.2026.102597

Scopus: View on Scopus

Document Type: Review

Authors and Affiliations

Aly D.M., Department of Clinical Chemistry, Theodor Bilharz Research Institute, Egypt; Fteah A.M., Department of Clinical Chemistry, Theodor Bilharz Research Institute, Egypt; Elrefaiy M.A., Hepato-gastroenterology Department, Theodor Bilharz Research Institute, Egypt; Seddik H.E., Hepato-gastroenterology Department, Theodor Bilharz Research Institute, Egypt

Abstract

Hepatocellular carcinoma (HCC) remains a formidable global health challenge, characterized by profound molecular heterogeneity and dismal survival rates when diagnosed at advanced stages. Despite extensive discovery of genetic and epigenetic alterations in hepatocellular carcinoma, translation of molecular biomarkers into clinical practice remains limited. This review provides a critical, high-level synthesis of emerging genetic and epigenetic biomarkers in HCC. Mechanistically, we evaluate pivotal somatic alterations, including telomere maintenance (TERT promoter), cell cycle checkpoints (TP53), and Wnt/β-catenin signaling (CTNNB1). We further delineate the functional dimensions of epigenetic dysregulation, focusing on aberrant DNA methylation landscapes, m6 A RNA methylation (m6a) RNA modifications, and non-coding RNA (ncRNA) networks as key regulators of oncogenic signaling, tumor stemness, and immune evasion. Crucially, these molecular axes are appraised through the lens of liquid biopsy paradigms—specifically circulating tumor DNA (ctDNA) and exosomal microRNAs (miRNAs)—highlighting their utility in early surveillance, molecular stratification, and minimal residual disease (MRD) monitoring. Finally, we address the systemic challenges of biomarker implementation in resource-constrained, low- and middle-income countries (LMICs), emphasizing the imperative for assay standardization, cost reduction, and multi-omics synthesis to bridge the gap between experimental molecular oncology and real-world clinical practice. This review proposes a translational classification framework to prioritize HCC biomarkers according to clinical utility, validation status, and implementation feasibility. © 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Keywords

Biomarkers; Epigenetics; Hepatocellular carcinoma; Liquid biopsy; Low- and middle-income countries; Precision oncology; biological marker; circulating tumor DNA; microRNA; data mining; DNA methylation; epigenetic modification; epigenetic RNA modification; human; immune evasion; liver cell carcinoma; minimal residual disease; multiomics; neoplastic cell transformation; personalized cancer therapy; promoter region; review; RNA methylation; signal transduction; survival rate; telomere homeostasis

Citation Information

Scopus Citations: 0

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