CELL INTELLIGENCE · 肿瘤细胞治疗研究

This study investigates the potential of nuclear receptor corepressor 1 (NCOR1) as a diagnostic and prognostic biomarker for clear cell renal cell carcinoma (ccRCC). Through the analysis of data from The Cancer Genome Atlas and Gene Expression Omnibus databases, along with immunohistochemical testing of clinical samples, this study revealed that NCOR1 expression was significantly downregulated in ccRCC tissues when compared to normal tissues. This downregulation was also more pronounced in 11 other types of tumors. The results of functional enrichment analysis indicated that NCOR1-related differentially expressed genes played a role in cell cycle regulation. These findings imply that the downregulation of NCOR1 expression may facilitate the progression of ccRCC through cell cycle activation. Correlation analysis revealed a significant association between NCOR1 expression and immune cell infiltration in ccRCC tissues. Specifically, NCOR1 expression was positively correlated with natural killer cells, γδ T cells, and mast cells, and negatively correlated with NK CD56 bright cells and cytotoxic cells. Moreover, NCOR1 expression was positively correlated with immune checkpoint genes, including TIGIT, CTLA-4, TP53, and PTEN. Analysis of the DNA methylation status revealed an association between the methylation levels of four CpG islands within the NCOR1 gene and the prognosis of patients with ccRCC. Elevated methylation levels were indicative of poor overall survival (OS). Conversely, NCOR1 gene mutations were not common in ccRCC and were not associated with survival rates. Clinicopathological correlation analysis demonstrated that in patients with ccRCC, decreased NCOR1 expression was significantly associated with advanced T stage, pathological stage, histological grade, as well as poor OS, disease-specific survival, and progression-free interval. Multivariate Cox regression analysis further confirmed that NCOR1 was an independent protective factor for the prognosis of ccRCC. Additionally, ROC curve analysis demonstrated that NCOR1 had diagnostic value (AUC = 0.673). In the nomogram model, combining NCOR1 expression with clinical parameters effectively predicted the 1-year, 3-year, and 5-year survival rates of ccRCC patients. In summary, the expression of NCOR1 is reduced in ccRCC, and its expression level and methylation status are closely related to the progression, immune microenvironment, and prognosis of ccRCC. These findings indicate that NCOR1 has the potential to become a viable diagnostic and prognostic biomarker as well as therapeutic target for ccRCC.