The prognostic value and immune correlation of IL18 expression and promoter methylation in renal cell carcinoma.
The prognostic value and immune correlation of IL18 expression and promoter methylation in renal cell carcinoma.
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DOI：
10.1186/s13148-023-01426-8
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发表时间：
2023-01-28
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
--
作者：
肾细胞癌（RCC）对免疫治疗不敏感，预后差。DNA甲基化调控基因表达，其异常变化与人类多种疾病有关。最近，DNA甲基化已被发现参与各种癌症的免疫浸润。然而，其在RCC中的模式仍然知之甚少。我们发现，与正常癌旁组织相比，IL 18在RCC肿瘤组织中显著过表达。IL 18启动子区低甲基化，这与IL 18 mRNA表达升高密切相关，并预测了晚期临床病理特征和较短的总生存期。此外，我们发现，在RCC肿瘤组织中，IL 18启动子甲基化与免疫检查点分子的下调和CD 8 + T细胞浸润的增加显著相关。我们已经确定了IL 18启动子甲基化和表达的重要作用，其与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相关。我们提出了IL 18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基本原理。在线版本包含补充材料，可通过10.1186/s13148-023-01426-8获得。
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. 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. 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. The online version contains supplementary material available at 10.1186/s13148-023-01426-8.
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DOI：
10.1038/s41571-020-00455-z
发表时间：
2021-04
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Braun DA;Bakouny Z;Hirsch L;Flippot R;Van Allen EM;Wu CJ;Choueiri TK
通讯作者：
Choueiri TK
影响因子：
15.9
作者：
Coughlin, CM;Salhany, KE;Lee, WMF
通讯作者：
Lee, WMF
影响因子：
4.7
作者：
Kang, Jae Seung;Bae, Seyeon Y.;Lee, Wang Jae
通讯作者：
Lee, Wang Jae
影响因子：
64.8
作者：
Mariathasan S;Turley SJ;Nickles D;Castiglioni A;Yuen K;Wang Y;Kadel EE III;Koeppen H;Astarita JL;Cubas R;Jhunjhunwala S;Banchereau R;Yang Y;Guan Y;Chalouni C;Ziai J;Şenbabaoğlu Y;Santoro S;Sheinson D;Hung J;Giltnane JM;Pierce AA;Mesh K;Lianoglou S;Riegler J;Carano RAD;Eriksson P;Höglund M;Somarriba L;Halligan DL;van der Heijden MS;Loriot Y;Rosenberg JE;Fong L;Mellman I;Chen DS;Green M;Derleth C;Fine GD;Hegde PS;Bourgon R;Powles T
通讯作者：
Powles T
影响因子：
11.5
作者：
Robertson, Michael J.;Kirkwood, John M.;Dar, Mohammed M.
通讯作者：
Dar, Mohammed M.