Comprehensive pan-cancer analysis identifies H2AFX associated with poor prognosis in lung adenocarcinoma

Objective: Lung adenocarcinoma (LUAD), the most prevalent histological subtype of lung cancer, develops through complex molecular regulatory networks. Despite significant advances in targeted therapies, there remains a critical shortage of LUAD-specific biomarkers successfully translated to clinical practice. This study aims to investigate the role of H2AFX, an essential histone H2A variant involved in maintaining genomic stability and chromatin remodeling, in LUAD pathogenesis and its clinical relevance. Methods: We employed an integrated bioinformatics approach using R programming and multiple public databases. Genetic alterations and expression profiles of H2AFX were analyzed through cBioPortal, TIMER2, Sangboxer, and TCGA databases. Advanced bioinformatics tools including TISIDB, ESTIMATE, and CIBERSORT were utilized to assess H2AFX's clinical correlations, prognostic value, and impact on the tumor immune microenvironment. Results: Our analysis revealed H2AFX's significant involvement in regulating the tumor microenvironment and immune modulation. Clinical investigations demonstrated that H2AFX overexpression strongly correlates with poor clinical outcomes in LUAD patients, establishing its independent prognostic significance. Conclusion: H2AFX shows substantial therapeutic potential in precision medicine and represents a promising dual-purpose biomarker for both prognostic assessment and immunological characterization in LUAD.