Elevated Expression of CHAF1A in Hepatocellular Carcinoma Progression and Immune Modulation

Clin Exp Gastroenterol. 2025 Apr 17:18:25-40. doi: 10.2147/CEG.S500029. eCollection 2025.

Abstract

Purpose: This study aimed to explore the role of CHAF1A in hepatocellular carcinoma (HCC) progression, focusing on its expression, co-expression genes, genomic alterations, promoter methylation, clinical relevance, prognostic value, and immune associations.

Methods: CHAF1A mRNA expression was analyzed using UALCAN. Co-expression genes and functions were explored via LinkedOmics. Genomic alterations were assessed using cBioPortal. Promoter methylation and clinical correlations were examined using GEO datasets. Prognostic significance was evaluated via Kaplan-Meier analysis. Immune cell infiltration and checkpoint gene associations were investigated.

Results: CHAF1A was significantly upregulated in HCC and involved in cancer-related pathways. Genomic alterations were prominent in T1-stage tumors, often linked to alcohol-related liver disease. Promoter methylation influenced HCC progression and prognosis. CHAF1A expression correlated with clinical characteristics (gender, stage, grade, etc.) and showed diagnostic potential (AUC = 0.795). High CHAF1A expression predicted poor prognosis across various subgroups and was positively associated with immune cell infiltration and checkpoint genes.

Conclusion: CHAF1A plays a critical role in HCC progression, with elevated expression linked to poor prognosis and immune modulation. These findings highlight its potential as a therapeutic target for HCC.

Keywords: CHAF1A; HCC; expression patterns; gene; immune cell infiltration.