Peptidylprolyl Isomerase a Regulates DNA Damage Repair and Serves as a Prognostic Biomarker in Lung Adenocarcinoma

This study investigated the role of peptidylprolyl isomerase A (PPIA) in lung adenocarcinoma (LUAD) using bioinformatics approaches and experimental validation.

This study began by assessing PPIA expression and its prognostic significance in LUAD. We then performed functional enrichment analyses and examined CNVs, DNA methylation, DNMT activity, RNA modification, immune cell infiltration, and drug therapy efficacy. Cellular experiments were performed to confirm the role of PPIA in DNA damage repair.

PPIA was overexpressed in LUAD tissues and was associated with poor prognosis, including shorter overall survival and progression-free interval. PPIA expression was correlated with CNVs, DNA methylation, DNMT activity, and RNA modification-related genes. It was also negatively associated with immune cell infiltration and immune-related gene expression, suggesting a potential immunosuppressive role. Drug sensitivity analysis indicated that PPIA may serve as a predictive biomarker for therapeutic efficacy in LUAD. In addition, PPIA expression was associated with DNA damage repair-related genes. Cellular experiments show that PPIA knockdown increases radiosensitivity and γ-H2AX foci formation, whereas PPIA overexpression exerts the opposite effects.

This study highlights the potential of PPIA as a prognostic biomarker and target in LUAD, particularly in the regulation of DNA damage repair and tumor immune microenvironment remodeling.