IL18 表达和启动子甲基化在肾细胞癌中的预后价值及其与免疫的相关性。

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.

背景：肾细胞癌（RCC）对免疫疗法不敏感，预后不良。DNA 甲基化调节基因表达，其异常变化与许多人类疾病有关。最近，人们发现 DNA 甲基化参与了各种癌症的免疫浸润。然而，其在 RCC 中的模式仍知之甚少。

结果：我们发现，与正常相邻组织相比，RCC 肿瘤组织中 IL18 表达明显上调，IL18 启动子区域低甲基化，与升高的 IL18 mRNA 表达强烈相关，并预测了先进的临床病理特征和较短的总生存期。此外，我们发现 IL18 启动子甲基化与 RCC 肿瘤组织中免疫检查点分子的下调和 CD8+T 细胞浸润的增加密切相关。

结论：我们确定了 IL18 启动子甲基化和表达的重要作用，它们与 RCC 的临床病理特征、总生存期、免疫细胞浸润和免疫检查点分子的表达有关。我们提出了 IL18 启动子甲基化作为预测 RCC 对免疫检查点抑制剂反应的分子生物标志物的原理。