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基于免疫相关基因的膀胱癌预后指数的鉴定与验证

Identification and validation of an immune-related gene-based prognostic index for bladder cancer.

作者信息

Tian Zijian, Meng Lingfeng, Long Xingbo, Diao Tongxiang, Hu Maolin, Wang Miao, Liu Ming, Wang Jianye

机构信息

Department of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences Beijing 100730, China.

Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences China.

出版信息

Am J Transl Res. 2020 Sep 15;12(9):5188-5204. eCollection 2020.

Abstract

Bladder cancer (BLCA) is a common malignancy arising from the urinary bladder and therapeutic options are limited. However, the mechanisms underlying BLCA development are poorly understood. In this study, robust rank aggregation was used to integrate five GEO BLCA microarray datasets for identifying differentially expressed genes (DEGs) between non-muscular invasive BLCA and muscular invasive BLCA. One-hundred fifty-four DEGs related to the degree of BLCA infiltration, including 24 immune-related genes (IRGs), were identified. Missense mutations were the most common type in IRGs. Ten hub IRGs were identified by protein-protein interaction network analysis. Gene set enrichment analysis and gene set variation analysis of two novel BLCA-related genes ( and ) revealed that they were related to immunity. Nine survival-related IRGs were identified, and their potential regulation by transcription factors was analyzed. An immune-related gene-based prognostic index (IRGPI) comprising , , , , , and was constructed using multivariate analysis. The reliability of the IRGPI was evaluated using independent datasets, and correlations between the IRGPI and clinicopathological characteristics, as well as the immune microenvironment, were evaluated. Finally, a nomogram was established to evaluate the prognosis of patients with BLCA. Our data provide new insights into the pathogenesis of BLCA and target genes for immunotherapy. The application of molecular markers for hierarchical prediction paves the way for precision medicine.

摘要

膀胱癌(BLCA)是一种起源于膀胱的常见恶性肿瘤,治疗选择有限。然而,BLCA发生的潜在机制尚不清楚。在本研究中,使用稳健秩聚合方法整合了五个GEO BLCA微阵列数据集,以鉴定非肌层浸润性BLCA和肌层浸润性BLCA之间的差异表达基因(DEG)。鉴定出154个与BLCA浸润程度相关的DEG,其中包括24个免疫相关基因(IRG)。错义突变是IRG中最常见的类型。通过蛋白质-蛋白质相互作用网络分析鉴定出10个核心IRG。对两个新的BLCA相关基因(和)进行基因集富集分析和基因集变异分析,结果表明它们与免疫相关。鉴定出9个与生存相关的IRG,并分析了它们受转录因子的潜在调控。使用多变量分析构建了一个基于免疫相关基因的预后指数(IRGPI),该指数由、、、、和组成。使用独立数据集评估IRGPI的可靠性,并评估IRGPI与临床病理特征以及免疫微环境之间的相关性。最后,建立了一个列线图来评估BLCA患者的预后。我们的数据为BLCA的发病机制和免疫治疗的靶基因提供了新的见解。分子标志物在分层预测中的应用为精准医学铺平了道路。

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