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整合分析鉴定凝血相关基因特征在透明细胞肾细胞癌中的预后和免疫治疗作用。

Integrated analysis to identify the prognostic and immunotherapeutic roles of coagulation-associated gene signature in clear cell renal cell carcinoma.

机构信息

Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.

Department of Urology, Peking University First Hospital, Beijing, China.

出版信息

Front Immunol. 2023 Mar 17;14:1107419. doi: 10.3389/fimmu.2023.1107419. eCollection 2023.

Abstract

The coagulation system is closely related to the physiological status and immune response of the body. Recent years, studies focusing on the association between coagulation system abnormalities and tumor progression have been widely reported. In clear cell renal cell carcinoma (ccRCC), poor prognosis often occurs in patients with venous tumor thrombosis and coagulation system abnormalities, and there is a lack of research in related fields. Significant differences in coagulation function were also demonstrated in our clinical sample of patients with high ccRCC stage or grade. Therefore, in this study, we analyzed the biological functions of coagulation-related genes (CRGs) in ccRCC patients using single-cell sequencing and TCGA data to establish the 5-CRGs based diagnostic signature and predictive signature for ccRCC. Univariate and multivariate Cox analyses suggested that prognostic signature could be an independent risk factor. Meanwhile, we applied CRGs for consistent clustering of ccRCC patients, and the two classes showed significant survival and genotype differences. The differences in individualized treatment between the two different subtypes were revealed by pathway enrichment analysis and immune cell infiltration analysis. In summary, we present the first systematic analysis of the significance of CRGs in the diagnosis, prognosis, and individualized treatment of ccRCC patients.

摘要

凝血系统与机体的生理状态和免疫反应密切相关。近年来,关于凝血系统异常与肿瘤进展之间关系的研究备受关注。在透明细胞肾细胞癌(ccRCC)中,静脉肿瘤血栓和凝血系统异常的患者往往预后不良,相关领域的研究还很缺乏。我们对高分期或高分级 ccRCC 患者的临床样本进行分析,结果显示凝血功能存在显著差异。因此,本研究利用单细胞测序和 TCGA 数据,分析了 ccRCC 患者的凝血相关基因(CRGs)的生物学功能,建立了基于 5 个 CRGs 的 ccRCC 诊断和预测特征。单因素和多因素 Cox 分析表明,预后特征可作为独立的危险因素。同时,我们应用 CRGs 对 ccRCC 患者进行一致性聚类,两类患者的生存和基因型差异显著。通过通路富集分析和免疫细胞浸润分析揭示了两种不同亚型之间的个体化治疗差异。综上所述,我们首次系统地分析了 CRGs 在 ccRCC 患者诊断、预后和个体化治疗中的意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bc5/10063824/0b3acc4ca362/fimmu-14-1107419-g001.jpg

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