Multi-omics Analysis of METTL2A as a Diagnostic Biomarker and Therapeutic Target in Hepatocellular Carcinoma

Objective To investigate the expression of METTL2A in hepatocellular carcinoma (LIHC) and analyze its correlation with clinical stage, prognosis, therapeutic response, and immune infiltration.Methods Differential mRNA expression of METTL2A between normal liver tissues and LIHC was assessed using the TCGA & GTEx databases. The diagnostic performance of METTL2A was evaluated through receiver operating characteristic (ROC) curve analysis using the pROC package in R. Logistic regression analyzed the association between METTL2A mRNA expression and clinicopathological characteristics of LIHC. Single-cell transcriptomics and spatial transcriptomics were employed to examine METTL2A expression patterns in tumor tissues and other cellular compartments. Kaplan-Meier survival analysis and Cox proportional hazards regression models were applied to assess the prognostic significance of METTL2A mRNA expression in LIHC patients. Gene Set Enrichment Analysis (GSEA) was performed to identify key functional pathways associated with METTL2A. Drug sensitivity correlations were investigated using GDSC2. Additionally, TISIDB and SangerBox were utilized to explore the relationship between METTL2A and immune microenvironment features in LIHC.Results METTL2A expression was significantly elevated at both mRNA and protein levels in LIHC compared to normal liver tissues (ROC AUC = 0.844). High METTL2A expression correlated with advanced pathological stage, higher clinical grade, aggressive molecular subtypes, and unfavorable prognosis. GSEA revealed METTL2A's predominant involvement in cell cycle regulation and DNA repair pathways. Immune landscape analysis demonstrated significant associations between METTL2A and MHC molecules, immune checkpoints, tumor mutational burden (TMB), and microsatellite instability (MSI).Conclusion METTL2A represents a potential diagnostic biomarker, prognostic indicator, and therapeutic target for personalized LIHC treatment strategies.