Integrating single-cell and spatial transcriptomics with pan-cancer bulk sequencing identifies OSR2 as a multifaceted biomarker for prognosis and tumor immunity.

[BACKGROUND] OSR2 plays a key role in various physiological processes and cancer development. Although interest in OSR2’s role in cancer is increasing, its mechanisms and clinical importance are not fully understood. This study thoroughly examines OSR2 gene expression in different cancers and evaluates its potential as a prognostic marker and therapeutic target.

[METHODS] A comprehensive pan-cancer analysis utilized single-cell RNA sequencing data from the CIDE database to examine OSR2 expression in various immune cells. Spatial transcriptomics from the CROST database explored OSR2’s spatial expression in renal carcinoma tissues. RNA sequencing data from the TCGA database assessed OSR2’s differential expression in 38 cancer types. The clinical significance of OSR2 was evaluated through its correlation with patient survival outcomes. Additionally, its impact on the tumor immune microenvironment was studied by analyzing associations with immunomodulatory factors, immune checkpoint molecules, and immune cell abundance.

[RESULTS] The pan-cancer analysis revealed that OSR2 expression is often altered in various cancers. It is upregulated in 13 types, notably in gliomas like glioblastoma multiforme and low-grade glioma, and downregulated in 19 types, including kidney and bladder cancers. High OSR2 levels are linked to poor prognosis in several cancers and correlate with clinical factors such as age, gender, and tumor stage. Immunologically, OSR2 expression is positively associated with immunomodulatory and checkpoint genes in cancers like gliomas and colon cancer, but shows an antagonistic relationship with immune cell infiltration in prostate and pancreatic cancers.

[CONCLUSION] The findings suggest that OSR2 expression varies across cancer types and is linked to patient prognosis and changes in the tumor immune environment, making it a promising therapeutic target. Its role in tumor progression and immune interactions indicates its potential as a biomarker for cancer immunotherapy. Further research is needed to understand OSR2’s molecular mechanisms in cancer and to validate its use in immunotherapy.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1007/s12672-026-04595-z.