Pan-cancer analysis of OSR2 with a focus on underlying mechanisms and therapeutic implications in lung adenocarcinoma
Shijie Liu1, Xuan Xiang2, Siyu Liu1
1Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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.
Insights
Odd-skipped related 2 (OSR2) promotes cancer progression by interacting with cancer-associated fibroblasts and inducing epithelial-mesenchymal transition. OSR2 is a potential prognostic biomarker and therapeutic target, particularly for lung adenocarcinoma (LUAD) immunotherapy response.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genomics
Background:
- The role of Odd-skipped related 2 (OSR2) in cancer pathogenesis is largely undefined.
- Preliminary studies suggest OSR2's involvement in solid tumor invasion and metastasis.
- Comprehensive analysis is needed to understand OSR2's function in the tumor microenvironment, its prognostic value, and predictive potential for immunotherapy response.
Purpose of the Study:
- To conduct an integrated pan-cancer analysis of OSR2.
- To evaluate OSR2 expression patterns, prognostic significance, and correlations with tumor mutational burden (TMB), microsatellite instability (MSI), and immune infiltration.
- To explore OSR2's functional roles in lung adenocarcinoma (LUAD) and its association with cancer-associated fibroblasts (CAFs).
Main Methods:
- Utilized TCGA and GEO datasets for integrated pan-cancer analysis of OSR2.
- Assessed OSR2 expression, prognostic value, TMB, MSI, immune infiltration, and immune checkpoint gene expression.
- Performed gene set enrichment analysis and in vitro experiments in LUAD models.
Main Results:
- OSR2 expression varied across cancers, with higher levels linked to poorer prognosis in several malignancies.
- OSR2 expression strongly correlated with cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME).
- OSR2 may promote tumor progression via epithelial-mesenchymal transition (EMT); OSR2 knockdown suppressed LUAD cell proliferation and migration.
Conclusions:
- OSR2 plays a key role in tumor biology and TME regulation.
- OSR2 is a potential prognostic biomarker and therapeutic target for various human cancers.
- OSR2 may predict immunotherapy response in LUAD.
