What question did this study set out to answer?

The aim is to evaluate the role of gene signatures and liquid biopsies in HCC prognostication and immunotherapy responses.

April 25, 2026Gene Expression0 citationsOpen Access

Emerging Roles of Hepatocellular Carcinoma Gene Signatures in Prognosis and Immunotherapy: Challenges and Opportunities

AWAmany Wahb GAGhada A. Abdel‐Aleem NSNoha O. Shawky

Key Points

The aim is to evaluate the role of gene signatures and liquid biopsies in HCC prognostication and immunotherapy responses.
Comprehensive review of genetic and epigenetic signatures in HCC.
Evaluation of multi-omics approaches to identify prognostic biomarkers.
Analysis of challenges in clinical validation and data standardization.
Identified gene signatures that reliably predict HCC prognosis and immunotherapy response.
Liquid biopsy technologies offer promising non-invasive monitoring for tumor evolution.
Challenges in data reproducibility and clinical application of genetic biomarkers remain.

Abstract

Hepatocellular carcinoma (HCC) remains one of the most fatal cancers, primarily due to late diagnosis and the lack of effective early biomarkers. Recent advances in multi-omics and liquid biopsy technologies hold promise for improving early detection, prognostication, and monitoring of HCC. Understanding the immune landscape of HCC through genetic and epigenetic signatures is essential for identifying therapeutic targets and improving immunotherapy outcomes. This review aims to present current findings on immune-related biomarkers, multi-omics strategies, and biomarker validation in HCC. It also aims to evaluate the role of liquid biopsy and gene signatures in predicting treatment responses, with a specific focus on their applications in immunotherapy. The goal is to provide a comprehensive framework for integrating these emerging tools into clinical practice. The integration of multi-omics approaches has led to the identification of robust gene signatures that predict HCC prognosis and response to immune checkpoint inhibitors. Liquid biopsy technologies, including circulating tumor DNA, provide non-invasive alternatives for monitoring tumor evolution and therapeutic responses. Despite promising results, challenges remain in clinical validation, particularly in cross-platform reproducibility and the interpretation of complex multi-omics data. While genetic biomarkers are rapidly advancing, their clinical application in personalized medicine remains hindered by technical and ethical challenges, such as data privacy, informed consent, and method standardization. The integration of multi-omics data and liquid biopsies offers a promising path toward real-time, personalized treatment and the development of universal prognostic signatures for HCC. However, successful clinical adoption depends on cross-disciplinary collaboration to standardize data protocols and overcome challenges regarding accuracy, reproducibility, and patient privacy.

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