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鉴定免疫相关长链非编码 RNA 以预测膀胱癌的预后和免疫治疗反应。

Identification of immune-related LncRNA for predicting prognosis and immunotherapeutic response in bladder cancer.

机构信息

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

Institute of Urology, Peking University, Beijing, China.

出版信息

Aging (Albany NY). 2020 Nov 18;12(22):23306-23325. doi: 10.18632/aging.104115.

Abstract

Long noncoding RNAs (lncRNAs) have multiple functions in the cancer immunity response and the tumor microenvironment. To investigate the immune-related lncRNA (IRlncRNA) signature for predicting prognosis and immunotherapeutic response in bladder cancer (BLCA), we extracted BLCA data from The Cancer Genome Atlas (TCGA) database. Finally, a total of 405 cases were enrolled and 8 prognostic IRlncRNAs (, , , were identified in the training set. Risk scores were calculated to divide patients into high-risk and low-risk groups, and the high-risk patients tended to have a poor overall survival (OS). Multivariate Cox regression analysis confirmed that the IRlncRNA signature could be an independent prognostic factor. The results were subsequently confirmed in the validating set. Additionally, this 8-IRlncRNA classifier was related to recurrence free survival (RFS) of BLCA. Functional characterization revealed this signature mediated immune-related phenotype. This signature was also associated with immune cell infiltration (i.e., macrophages M0, M2, Tregs, CD8 T cells, and neutrophils) and immune checkpoint inhibitors (ICIs) immunotherapy-related biomarkers [mismatch repair (MMR) genes, tumor mutation burden (TMB) and immune checkpoint genes]. The present study highlighted the value of the 8-IRlncRNA signature as a predictor of prognosis and immunotherapeutic response in BLCA.

摘要

长链非编码 RNA(lncRNA)在癌症免疫反应和肿瘤微环境中具有多种功能。为了研究与免疫相关的 lncRNA(IRlncRNA)特征,以预测膀胱癌(BLCA)的预后和免疫治疗反应,我们从癌症基因组图谱(TCGA)数据库中提取了 BLCA 数据。最终,共纳入 405 例患者,在训练集中鉴定出 8 个预后相关的 IRlncRNA(,,, 。计算风险评分以将患者分为高风险和低风险组,高风险患者的总体生存(OS)倾向较差。多因素 Cox 回归分析证实,IRlncRNA 特征可以作为独立的预后因素。该结果随后在验证集中得到了证实。此外,该 8-IRlncRNA 分类器与 BLCA 的无复发生存(RFS)相关。功能特征分析表明,该特征介导了与免疫相关的表型。该特征还与免疫细胞浸润(即巨噬细胞 M0、M2、Tregs、CD8 T 细胞和中性粒细胞)和免疫检查点抑制剂(ICIs)免疫治疗相关生物标志物(如错配修复(MMR)基因、肿瘤突变负荷(TMB)和免疫检查点基因)相关。本研究强调了 8-IRlncRNA 特征作为预测 BLCA 预后和免疫治疗反应的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8976/7746369/1e8e2c633415/aging-12-104115-g001.jpg

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