Comprehensive Analysis of KPNA2 as a Prognostic Biomarker in Lung Adenocarcinoma: Associations with Ferroptosis and Immune Infiltration

Background Lung adenocarcinoma (LUAD) is a leading cause of cancer-related mortality worldwide, with limited effective prognostic biomarkers available. Methods This study investigated the role of KPNA2 as a prognostic biomarker in LUAD and its associations with ferroptosis and immune infiltration via bioinformatics approaches. Differentially expressed genes (DEGs) linked to LUAD and ferroptosis were screened from GSE1987, GSE18842 and GeneCards, and hub genes were identified by PPI network analysis. KPNA2 expression was validated across TCGA, GEO and HPA databases, and its correlations with clinicopathological features, survival outcomes, 24 immune cell infiltration levels and ferroptosis-related genes were analyzed. Co-expressed genes of KPNA2 were explored using LinkedOmics and TCGA data. Results KPNA2 was significantly upregulated in LUAD tissues and associated with advanced tumor grade, clinical stage and shorter overall survival ( p  < 0.05). KPNA2 expression positively correlated with Th2 and T helper cell infiltration, and was closely associated with key ferroptosis-related genes (e.g., PTGS2, TFRC). Co-expression analysis revealed extensive functional links of KPNA2 with LUAD-related genes. Conclusion Our findings confirm that high KPNA2 expression predicts poor prognosis in LUAD, and KPNA2 may regulate LUAD progression by modulating immune infiltration and ferroptosis, serving as a potential prognostic biomarker and therapeutic target for LUAD.