研究动态
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铜中毒相关基因 DLAT 作为透明细胞肾细胞癌免疫治疗的预后生物标志物:多数据库和实验验证。

Cuproptosis-related gene DLAT serves as a prognostic biomarker for immunotherapy in clear cell renal cell carcinoma: multi-database and experimental verification.

发表日期:2023 Nov 07
作者: Shuaishuai Huang, Congbo Cai, Kena Zhou, Xue Wang, Xue Wang, Dong Cen, Guobin Weng
来源: Cell Death & Disease

摘要:

肾透明细胞癌(ccRCC)是最常见的肾癌类型。本研究旨在探讨铜死亡相关基因二氢硫辛酰胺S-乙酰转移酶(DLAT)在ccRCC中的预后和免疫治疗价值。DLAT的mRNA和蛋白表达及甲基化水平,以及DLAT与生存预后、临床特征的关系使用多个数据库评估 ccRCC 患者的生物学功能、免疫微环境和反应。此外,还对75对ccRCC组织样本和3种细胞系进行了实验验证。多个数据库的生物信息学分析、qRT-PCR和western blot验证了ccRCC中DLAT的表达低于癌旁组织。 DLAT低表达的患者生存率较低,临床预后较差,免疫细胞浸润和免疫抑制点表达较强,肿瘤免疫功能障碍和排斥(TIDE)评分较高。DLAT被确定为ccRCC的独立预后因素,与ccRCC患者的预后和免疫反应密切相关。
Renal clear cell carcinoma (ccRCC) is the most common type of renal cancer. Here we aim to explore the prognosis and immunotherapeutic value of copper death-related gene Dihydrolipoamide S-acetyltransferase (DLAT) in ccRCC.The mRNA and protein expressions and methylation level of DLAT, as well as the relation of DLAT to survival prognosis, clinical characteristics, biological function, and immune microenvironment and responses in patients with ccRCC were evaluated using multiple databases. In addition, 75 paired ccRCC tissue samples and 3 kinds of cell lines were tested for experimental validation.Bioinformatics analysis of multiple databases, qRT-PCR, and western blot verified that DLAT expression in ccRCC was lower than that in paracancerous tissues. Patients with low expression of DLAT had a lower survival rate, worse clinical prognosis, stronger immune cell infiltration and expression of immunosuppressive points, and higher tumor immune dysfunction and exclusion (TIDE) scores.DLAT was identified as an independent prognostic factor in ccRCC and was closely related to the prognosis and immune responses of patients with ccRCC.