肾透明细胞癌(ccRCC)是肾细胞癌(RCC)中最常见的亚型，患者的预后具有很大的变异性。内质网应激(ERS)是由内质网(ER)稳态紊乱引发的持续状态，已被证实能够控制恶性细胞中多条与肿瘤相关的通路，并动态重编程免疫细胞功能。本研究旨在鉴定与ERS相关的遗传风险标志(ERSGRS)，以改善ccRCC患者的生存预测。在本研究中，我们采用癌症基因组图谱(TCGA)的差异表达基因(DEGs)，通过最小绝对收缩和选择操作(LASSO)回归构建了具有独立预后意义的ERSGRS。根据风险评分将患者分为低风险组和高风险组后，生存分析显示低风险组的总生存期(OS)较高风险组更长，受试者工作特征曲线(ROC)分析证实了ERSGRS的强大预测能力。与此同时，高风险组的肿瘤微环境(TME)表现出免疫抑制性表型，出现了更多调节性T细胞(Tregs)和巨噬细胞浸润。而低风险组的TME则具有更强的抗肿瘤免疫潜力。总体而言，ERSGRS可能是ccRCC预后的有价值的预测工具。版权所有 © 2023 作者。由 Wolters Kluwer Health, Inc. 出版。

Clear-cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC), which exhibits great variability in the prognosis of patients. Endoplasmic reticulum stress (ERS) is a persistent state triggered by disruption of endoplasmic reticulum (ER) homeostasis, which has been shown to control multiple pro-tumor-associated pathways in malignant cells while dynamically reprogramming immune cell function. This study aimed to identify ERS-related genetic risk signatures (ERSGRS) to ameliorate survival prediction in ccRCC patients. In this study, we adopted differentially expressed genes (DEGs) from the Cancer Genome Atlas (TCGA) and constructed ERSGRS with independent prognostic significance by least absolute shrinkage and selection operator (LASSO) regression. After separation of patients based on risk score, survival analysis showed that low-risk patients had longer overall survival (OS) than high-risk patients, and receiver operating characteristic (ROC) curve analysis confirmed the strong predictive ability of ERSGRS. Meanwhile, the tumor microenvironment (TME) of the high-risk group demonstrated an immunosuppressive phenotype, with more infiltration of regulatory T cells (Tregs) and macrophages. The TME in the low-risk group had a stronger potential for anti-tumor immunity. Overall, the ERSGRS could be a valuable predictive tool for ccRCC prognosis.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.