The prognostic value and immune correlation of IL18 expression and promoter methylation in renal cell carcinoma

Background: Renal cell carcinoma (RCC) is not sensitive to immunotherapy and have poor prognosis. DNA methylation regulates gene expression, and its abnormal changes are related to many human diseases. Recently, DNA methylation has been found to participate in immune infiltration in various cancers. However, its pattern in RCC remains poorly understood. Results: : We found that IL18 was significantly over-expressed in RCC tumor tissues compared to normal adjacent tissues. The IL18 promoter region was hypomethylated, which was strongly correlated with elevated IL18 mRNA expression, and predicted advanced clinicopathological characteristics and shorter overall survival. Furthermore, we found that IL18 promoter methylation was significantly related to the down-regulation of immune checkpoint molecules and increase of CD8+ T cell infiltration in RCC tumor tissues. Conclusions: : We have identified the important role of IL18 promoter methylation and expression, which are associated with clinicopathological characteristics, overall survival, immune cell infiltration and expression of immune checkpoint molecules in RCC. We present the rationale for IL18 promoter methylation as a molecular biomarker for predicting the response of RCC to immune checkpoint inhibitors.