Stratification of Hepatocellular Carcinoma Using N⁶-Methyladenosine

Area of Science:

• Epigenetics and Cancer Biology
• Immunotherapy and Precision Medicine

Background:

• N6-methyladenosine (m6A) modification is a prevalent epigenetic mechanism in eukaryotes.
• m6A modification is implicated in the pathogenesis and progression of hepatocellular carcinoma (HCC).
• Understanding m6A's role is crucial for advancing HCC immunotherapy.

Purpose of the Study:

• To evaluate m6A-related genes for predicting overall survival in HCC patients.
• To assess the potential of m6A-related genes in predicting immunotherapy efficacy for HCC.
• To develop a prognostic risk model for HCC based on m6A regulators.

Main Methods:

• Transcriptomic data from TCGA-LIHC and GSE76427 (485 HCC patients) were used for training.
• Clustering analysis based on 23 m6A regulators identified HCC subtypes.
• LASSO Cox and multivariate Cox regression analyses constructed an 8-gene risk model; in vitro assays validated ANLN's role.

Main Results:

• An 8-gene risk score demonstrated accurate and stable prognostic assessment for HCC, validated internally and externally.
• High-risk scores correlated with elevated TP53 mutation frequency, TMB, stem cell characteristics, and poor prognosis.
• The signature predicted immunotherapy efficacy, with high-risk patients showing lower immune tolerance and better response to ICIs.

Conclusions:

• An 8-gene m6A signature effectively predicts prognosis and immunotherapy response in HCC patients.
• This signature can guide personalized treatment strategies and improve patient outcomes in HCC.
• The m6A-related gene ANLN promotes HCC cell proliferation and migration, highlighting its potential as a therapeutic target.