Pan-cancer analysis of OSR2 with a focus on underlying mechanisms and therapeutic implications in lung adenocarcinoma

Background The transcription factor Odd-skipped related 2 (OSR2) is involved in multiple physiological processes, yet its role in cancer pathogenesis remains largely undefined. Preliminary studies have suggested that OSR2 may contribute to the invasion and metastasis of several solid tumors. However, its function in the tumor microenvironment, its prognostic value and potential in predicting responses to immunotherapy across different cancer types are still inadequately explored and warrant a comprehensive systematic analysis. Methods We performed an integrated pan-cancer analysis of OSR2 utilizing data from TCGA and GEO. Our analysis systematically evaluated OSR2 expression patterns, prognostic significance, and its correlations with tumor mutational burden (TMB), microsatellite instability (MSI), immune infiltration and immune checkpoint gene expression. Gene set enrichment analysis was employed for pathway enrichment analysis in both the pan-cancer bulk RNA-seq and LUAD single-cell transcriptomic data. The functional roles of OSR2 in LUAD were further validated through in vitro experiments. Results OSR2 expression exhibited considerable heterogeneity across cancers, with elevated expression levels correlating with poor prognosis in several malignancies. Immune infiltration correlation and pan-cancer single-cell transcriptomics analysis revealed a strong association between OSR2 expression and cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME). Functional enrichment analysis suggested that OSR2 may promote tumor progression through induction of epithelial-mesenchymal transition (EMT). Furthermore, OSR2 knockdown attenuated the tumor-promoting effects of CAFs, resulting in suppressed proliferation and migration of LUAD cells in vitro. Conclusion Collectively, our findings highlight the key role of OSR2 in tumor biology and tumor microenvironment regulation. OSR2 emerges as a promising prognostic biomarker and potential therapeutic target for human cancers; additionally, it may act as a reliable predictor of immunotherapy response in LUAD.