Results for “OSR2” | Search PubMed

PubMed2026

Integrated pan-cancer profiling highlights OSR2 as a prognostic indicator and immune-associated biomarker.

BACKGROUND: Odd-skipped-related 2 (OSR2), encoded by the OSR2 gene, has been reported to function as a checkpoint associated with CD8⁺ T-cell exhaustion in the tumor microenvironment of solid malignancies, suggesting its potential as a therapeutic target to improve immunotherapeutic responses. Nevertheless, the molecular and clinical significance of OSR2 across diverse cancer types has not yet been systematically investigated, and its pan-cancer expression profile, prognostic implications, and associations with tumor immunity remain to be fully elucidated. METHODS: In this study, we integrated datasets from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx) portal, and the Human Protein Atlas to construct a systematic pan-cancer profile of OSR2. The prognostic value of OSR2 was comprehensively assessed using univariate Cox regression, survival analysis, and receiver operating characteristic (ROC) curve analysis. In addition, we performed an in-depth analysis of the relationships between OSR2 and multiple molecular and immunological features, including copy number variation (CNV), DNA methylation, tumor mutational burden (TMB), microsatellite instability (MSI), immune-related gene expression, immune cell infiltration, and drug sensitivity, with the aim of exploring its potential immunological associations with the tumor microenvironment. RESULTS: OSR2 expression was significantly upregulated or downregulated in the majority of tumor tissues relative to normal counterparts and exhibited distinct cancer-type-specific patterns across clinical stages. CNV alterations and aberrant DNA methylation were closely associated with abnormal OSR2 mRNA expression in multiple cancers. Prognostic analyses indicated that OSR2 expression was significantly associated with overall survival, disease-specific survival, disease-free interval, and progression-free interval across multiple cancer types, showing either risk-associated or protective associations in a tumor-context-dependent manner. Furthermore, OSR2 expression showed strong associations with immune cell infiltration, particularly T-cell subsets, and was significantly correlated with the expression of multiple immune checkpoint-related genes across diverse malignancies. OSR2 expression was also closely associated with TMB, MSI, and sensitivity to multiple anticancer agents. CONCLUSION: Taken together, these findings suggest that OSR2 is associated with prognosis and immune-related features across multiple cancer types. OSR2 may be linked to features of the tumor immune microenvironment through its relationships with immune cell infiltration, immune checkpoint gene expression, and genomic instability, and thus may serve as a candidate biomarker for further investigation in cancer immunotherapy.

CD8⁺ T-cell↗

PubMed2024

Hyd/UBR5 defines a tumor suppressor pathway that links Polycomb repressive complex to regulated protein degradation in tissue growth control and tumorigenesis.

Tumor suppressor genes play critical roles in normal tissue homeostasis, and their dysregulation underlies human diseases including cancer. Besides human genetics, model organisms such as Drosophila have been instrumental in discovering tumor suppressor pathways that were subsequently shown to be highly relevant in human cancer. Here we show that hyperplastic disc (Hyd), one of the first tumor suppressors isolated genetically in Drosophila and encoding an E3 ubiquitin ligase with hitherto unknown substrates, and Lines (Lin), best known for its role in embryonic segmentation, define an obligatory tumor suppressor protein complex (Hyd-Lin) that targets the zinc finger-containing oncoprotein Bowl for ubiquitin-mediated degradation, with Lin functioning as a substrate adaptor to recruit Bowl to Hyd for ubiquitination. Interestingly, the activity of the Hyd-Lin complex is directly inhibited by a micropeptide encoded by another zinc finger gene, drumstick (drm), which functions as a pseudosubstrate by displacing Bowl from the Hyd-Lin complex, thus stabilizing Bowl. We further identify the epigenetic regulator Polycomb repressive complex1 (PRC1) as a critical upstream regulator of the Hyd-Lin-Bowl pathway by directly repressing the transcription of the micropeptide drm Consistent with these molecular studies, we show that genetic inactivation of Hyd, Lin, or PRC1 resulted in Bowl-dependent hyperplastic tissue overgrowth in vivo. We also provide evidence that the mammalian homologs of Hyd (UBR5, known to be recurrently dysregulated in various human cancers), Lin (LINS1), and Bowl (OSR1/2) constitute an analogous protein degradation pathway in human cells, and that OSR2 promotes prostate cancer tumorigenesis. Altogether, these findings define a previously unrecognized tumor suppressor pathway that links epigenetic program to regulated protein degradation in tissue growth control and tumorigenesis.

Animals↗