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通过整合肾透明细胞癌患者的单细胞和批量RNA测序数据构建的一种新型内皮相关预后指数。

A novel endothelial-related prognostic index by integrating single-cell and bulk RNA sequencing data for patients with kidney renal clear cell carcinoma.

作者信息

Li Deng-Xiong, Yu Qing-Xin, Zeng Chui-Xuan, Ye Lu-Xia, Guo Yi-Qing, Liu Jun-Fei, Zheng Hai-Hong, Feng Dechao, Wei Wuran

机构信息

Department of Urology, West China Hospital, Institute of Urology, Sichuan University, Chengdu, Sichuan, China.

Department of Pathology, Taizhou Hospital, Wenzhou Medical University, Linhai, Zhejiang, China.

出版信息

Front Genet. 2023 Mar 10;14:1096491. doi: 10.3389/fgene.2023.1096491. eCollection 2023.

Abstract

Endothelial cells in the tumor microenvironment play an important role in the development of kidney renal clear cell carcinoma (KIRC). We wanted to further identify the function of endothelial cells in KIRC patients by integrating single-cell and bulk RNA sequencing data. Online databases provide the original data of this study. An endothelial-related prognostic index (ERPI) was constructed and validated by R version 3.6.3 and relative packages. The ERPI consisted of three genes (CCND1, MALL, and VWF). Patients with high ERPI scores were significantly correlated with worse prognosis than those with low ERPI scores in the TCGA training group, TCGA test group, and GSE29609 group. A positive correlation was identified between the ERPI score and poor clinical features. The results of functional analysis indicated that ERPI was significantly associated with immune-related activities. We suggested that patients with high ERPI scores were more likely to benefit from immunotherapy based on the results of immune checkpoints, tumor microenvironment, stemness index, and TCIA, while patients with low ERPI scores were sensitive to gemcitabine, docetaxel, paclitaxel, axitinib, pazopanib, sorafenib, and temsirolimus according to the results of the "pRRophetic" algorithm. Therefore, this ERPI may help doctors choose the optimal treatment for patients with KIRC. By integrating single-cell and bulk RNA sequencing data from KIRC patients, we successfully identified the key genes from the perspective of endothelial cells in the tumor microenvironment and constructed ERPIs that had positive implications in precision medicine.

摘要

肿瘤微环境中的内皮细胞在肾透明细胞癌(KIRC)的发展中起着重要作用。我们希望通过整合单细胞和批量RNA测序数据,进一步确定KIRC患者体内内皮细胞的功能。在线数据库提供了本研究的原始数据。利用R 3.6.3版本及相关软件包构建并验证了一个内皮相关预后指数(ERPI)。ERPI由三个基因(CCND1、MALL和VWF)组成。在TCGA训练组、TCGA测试组和GSE29609组中,ERPI评分高的患者与低ERPI评分的患者相比,预后明显更差。ERPI评分与不良临床特征之间存在正相关。功能分析结果表明,ERPI与免疫相关活动显著相关。基于免疫检查点、肿瘤微环境、干性指数和肿瘤免疫活性分析(TCIA)的结果,我们认为ERPI评分高的患者更有可能从免疫治疗中获益,而根据“pRRophetic”算法的结果,ERPI评分低的患者对吉西他滨、多西他赛、紫杉醇、阿昔替尼、帕唑帕尼、索拉非尼和替西罗莫司敏感。因此,这个ERPI可能有助于医生为KIRC患者选择最佳治疗方案。通过整合KIRC患者的单细胞和批量RNA测序数据,我们成功地从肿瘤微环境中内皮细胞的角度鉴定出关键基因,并构建了对精准医学有积极意义的ERPI。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a92/10036355/f37dafb530b9/fgene-14-1096491-g001.jpg

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