Prognostic significance and immune correlation of STING expression and promoter methylation in renal cell carcinoma

Renal cell carcinoma (RCC) typically shows resistance to immunotherapy and is associated with poor prognosis. Recent studies have revealed a role for DNA methylation in immune infiltration in different cancers, but its pattern in RCC is not well understood. In this study, we analyzed the relationships among STING promoter methylation, mRNA expression, overall survival, and immune cell infiltration in a TCGA cohort and validated the findings in an independent cohort. Additionally, we assessed these correlations in an RCC cohort from Sun Yat-sen University Cancer Center (SYSUCC) using immunohistochemistry and pyrosequencing. Our findings revealed significant hypomethylation of the STING promoter in RCC tumor tissues compared with normal tissues, which strongly correlated with increased STING mRNA expression across all three RCC cohorts. Additionally, hypomethylation of the STING promoter hypomethylation was associated with advanced clinicopathological features and poor overall survival. Moreover, we found a significant relationship between STING promoter methylation and both immune cell infiltration and the expression of immune checkpoint molecules. Our findings in the SYSUCC cohort confirmed that STING promoter methylation was related to CD4 and CD8 T-cell infiltration in RCC tumor tissues. These results suggest that methylation of the STING promoter plays a pivotal role in regulating its expression and influencing the tumor microenvironment. STING promoter methylation and expression are linked to clinicopathological characteristics, overall survival, and immune cell infiltration in RCC. We propose that further validation of STING promoter methylation represents a biomarker for predicting responses to immune checkpoint inhibitors in RCC.