BANF1 as a potential prognostic biomarker associated with tumor-intrinsic programs and a complex immune landscape in...

Lung adenocarcinoma (LUAD) remains a major cause of cancer mortality, highlighting the need for biomarkers that integrate tumor-intrinsic biology with immune contexture. Barrier-to-autointegration factor 1 (BANF1), a chromatin-associated protein involved in nuclear envelope assembly and DNA damage response, has been implicated in tumor progression, yet its role in LUAD is incompletely defined. Here, we performed integrated analyses of TCGA and GEO datasets, pharmacogenomic resources (CTRP and GDSC), and in vitro functional experiments to characterize BANF1 in LUAD. BANF1 was significantly upregulated in LUAD tissues and independently associated with unfavorable overall survival across multiple cohorts. A prognostic nomogram incorporating BANF1 improved risk stratification beyond clinical stage alone. Promoter hypomethylation was observed in tumors and may contribute to increased BANF1 expression. Immune profiling revealed a heterogeneous microenvironment in BANF1-high tumors. Although ESTIMATE scores suggested reduced overall immune and stromal content, CIBERSORT analysis demonstrated enrichment of CD8⁺ T cells, M1 macrophages, follicular helper T cells, and regulatory T cells, together with selective upregulation of immune checkpoint genes. BANF1 expression positively correlated with tumor mutational burden but not microsatellite instability, and associations with immunotherapy response were context dependent. Pharmacogenomic analyses indicated lower IC50 values, suggesting increased drug sensitivity in LUAD cell line models. Gene set enrichment analysis identified replication- and oxidative phosphorylation-related programs in the BANF1-high group. Functionally, BANF1 knockdown suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition while promoting apoptosis. Collectively, BANF1 represents an independent prognostic biomarker in LUAD and is associated with proliferative transcriptional programs and a complex immune landscape. Its relationships with immunotherapy-related features were context dependent and partly based on non-LUAD cohorts, and thus should be interpreted as tumor-type-specific and hypothesis-generating.