m6A regulators-based gene expression pattern is associated with immune microenvironment characteristics in...

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• N6-methyladenosine (m6A) modification is crucial in cancer development.
• The role of m6A regulators in hepatocellular carcinoma (HCC) and its immune microenvironment is not fully understood.

Purpose of the Study:

• To investigate the association between m6A modification-related genes and the HCC immune microenvironment.
• To assess the potential of targeting m6A regulators for improving HCC immunotherapy.

Main Methods:

• Utilized RNA sequencing and clinical data from TCGA and ICGC databases for 23 m6A regulators.
• Employed ConsensusClusterPlus for sample clustering, Cox and LASSO regression for risk model development.
• Applied ESTIMATE, ssGSEA, and immunohistochemistry to analyze immune microenvironment and PD-L1 expression.

Main Results:

• HCC samples clustered into three groups based on m6A regulators, with Cluster 3 showing poorer prognosis.
• A 4-gene risk model (DNTTIP2, SEPHS1, TCOF1, TXLNA) was established, correlating with HCC immune microenvironment and serving as an independent prognostic factor.
• Higher METTL3 and YTHDF1 expression correlated with increased PD-L1 levels in HCC tissues.

Conclusions:

• m6A modification significantly impacts the HCC immune microenvironment.
• Targeting m6A regulators presents a potential strategy to overcome immune escape in HCC and enhance immunotherapy efficacy.