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

Abstract

Background Renal cell carcinoma (RCC) is not sensitive to immunotherapy and has 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.

Identification and analysis of chemokine-related and NETosis-related genes in acute pancreatitis to develop a predictive model

“…IL18 was first described as an endotoxin-induced serum factor. As part of the IL1 family, IL18 can stimulate systemic and local inflammation by releasing TNF-α, COX2, and GM-CSF ( Wang X. et al, 2023 ). Emerging research indicated that IL-18 plays a significant regulatory role in immunoregulation across various inflammatory and malignant conditions.…”

The Role of IL-18 in P2RX7-Mediated Antitumor Immunity

“…IL-18 would have a different effect depending on the cell type, which demonstrated by the facts that human pancreatic tumor tissue expresses high levels of IL-18 [152,153,156,157] and low levels of IL-18BP [156] and these are linked to shorter survival and increased metastasis, whereas high levels of plasmatic IL-18 are associated with a better outcome [152]. Similarly, NLRP3-associated IL-18 is found in high levels in plasma of lymphoma [142] and multiple myeloma patients where IL-18 is a predictor of poor survival in multiple myeloma patients [149,158], esophageal carcinoma [159], renal cell carcinoma [160] and gastric carcinoma [161]. High expression of IL-18 is also associated with increased metastases in hepatocellular and breast carcinomas [162,163].…”