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焦亡在肾透明细胞癌免疫治疗和靶向治疗中的潜在应用

Potential Application of Pyroptosis in Kidney Renal Clear Cell Carcinoma Immunotherapy and Targeted Therapy.

作者信息

Qi Xiaochen, Che Xiangyu, Li Quanlin, Wang Qifei, Wu Guangzhen

机构信息

Department of Urology, First Affiliated Hospital, Dalian Medical University, Dalian, China.

出版信息

Front Pharmacol. 2022 Jun 15;13:918647. doi: 10.3389/fphar.2022.918647. eCollection 2022.

Abstract

Renal cell carcinoma (RCC) is a type of cancer with an increasing rate of morbidity and mortality and is a serious threat to human health. The treatment of RCC, especially kidney renal clear cell carcinoma (KIRC), has always been the focus of clinical treatment. Using The Cancer Genome Atlas (TCGA) database as a starting point, we explored the feasibility of applying the pyroptosis mechanism to KIRC treatment by searching for cancer markers associated with pyroptosis and cancer treatment signatures. The obtained samples were clustered using unsupervised clustering analysis to define the different KIRC subtypes with different pyroptosis expression levels. Based on this, a gene expression analysis was performed to explore the carcinogenic mechanism that is markedly related to pyroptosis. The Genomics of Drug Sensitivity in Cancer database and single sample gene set enrichment analysis (ssGSEA) algorithm were used to analyze the different treatment methods of the current prominent KIRC to determine whether pyroptosis plays a role. Finally, LASSO regression was used to screen for related genes and construct a model to predict patient prognosis. The expression levels of GSDME, CASP3, CASP4, CASP5, CHMP3, and CHMP4C were incorporated into the model construction. After verification, the prediction accuracy of the 3-, 5-, 7- and 10 years survival rates of our prognostic model were 0.66, 0.701, 0.719, and 0.728, respectively. Through the above analysis, we demonstrated the feasibility of pyroptosis in the clinical treatment of KIRC and provided novel ideas and suggestions for the clinical treatment of KIRC.

摘要

肾细胞癌(RCC)是一种发病率和死亡率不断上升的癌症类型,对人类健康构成严重威胁。RCC的治疗,尤其是肾透明细胞癌(KIRC)的治疗,一直是临床治疗的重点。以癌症基因组图谱(TCGA)数据库为起点,我们通过寻找与细胞焦亡和癌症治疗特征相关的癌症标志物,探索将细胞焦亡机制应用于KIRC治疗的可行性。使用无监督聚类分析对获得的样本进行聚类,以定义具有不同细胞焦亡表达水平的不同KIRC亚型。在此基础上,进行基因表达分析,以探索与细胞焦亡显著相关的致癌机制。利用癌症药物敏感性基因组学数据库和单样本基因集富集分析(ssGSEA)算法,分析当前突出的KIRC的不同治疗方法,以确定细胞焦亡是否发挥作用。最后,使用LASSO回归筛选相关基因并构建模型来预测患者预后。将GSDME、CASP3、CASP4、CASP5、CHMP3和CHMP4C的表达水平纳入模型构建。经过验证,我们的预后模型对3年、5年、7年和10年生存率的预测准确率分别为0.66、0.701、0.719和0.728。通过上述分析,我们证明了细胞焦亡在KIRC临床治疗中的可行性,并为KIRC的临床治疗提供了新的思路和建议。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d86/9252305/31ca41ce04ed/fphar-13-918647-g001.jpg

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