Identification of a C2H2 zinc finger-related lncRNA prognostic signature and its association with the immune microenvironment in clear cell renal cell carcinoma.

IF 1.9 3区 医学 Q4 ANDROLOGY
Translational andrology and urology Pub Date : 2025-02-28 Epub Date: 2025-02-25 DOI:10.21037/tau-2024-769
Ting Tian, Cheng Shen, Łukasz Zapała, Xingxing Fang, Bing Zheng
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引用次数: 0

Abstract

Background: Clear cell renal cell carcinoma (ccRCC) is the main component of renal cell carcinoma, and advanced ccRCC often predicts a poor prognosis. In recent years, research has revealed the critical role of Cys2His2 zinc finger genes (CHZFs) and long non-coding RNAs (lncRNAs) in the development of cancer. Currently, little is known about the prognostic value of the lncRNAs linked to Cys2His2 (C2H2) zinc finger proteins (ZFPs) in ccRCC. The aim of this study was to construct a prognostic model for C2H2-associated lncRNAs to assist in the selection of clinical therapy.

Methods: RNA-sequencing data, and related clinical and prognostic information were downloaded from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analyses were conducted to identify Cys2His2 zinc finger-associated long non-coding RNAs (CHZFLs) and build prediction signatures. A receiver operating characteristic (ROC) curve analysis was performed to validate the risk model. The prognosis of the groups was analyzed using the Kaplan-Meier method. The independent prognostic significance of these signatures was evaluated by univariate and multivariate Cox regression analyses. The relationship between the CHZFL signature and ccRCC tumor immunity was confirmed by a differential analysis of immune function and immunological checkpoints.

Results: A signature composed of five lncRNAs (AL117336.2, AC026401.3, AC124854.1, DBH-AS1, and LINC02100) was constructed. The results revealed a strong correlation between the CHZFLs signature and the prognosis of ccRCC patients. Prognostic characteristics of CHZFLs are independent prognostic factors in ccRCC patients. The diagnostic efficacy of the predictive signature was higher than that of individual clinicopathologic variables, and it had a ROC area under the curve (AUC) of 0.775. The results of the clinical subgroup analysis showed that the high-risk group had shorter overall survival (OS) than the low-risk group. Common chemotherapy medications, including vinorelbine, cytarabine, epirubicin, and gemcitabine, caused increased sensitivity in the high-risk group. Additionally, the single-sample gene set enrichment analysis (ssGSEA) revealed that the immunological state of the ccRCC patients was substantially linked with the predictive parameters.

Conclusions: The five CHZFL signature can help predict the prognosis of ccRCC patients, and assist in selecting immunotherapy and chemotherapy regimens in clinical practice.

鉴定C2H2锌指相关lncRNA预后特征及其与透明细胞肾细胞癌免疫微环境的关系
背景:透明细胞肾细胞癌(Clear cell renal cell carcinoma, ccRCC)是肾细胞癌的主要组成部分,晚期的ccRCC往往预后较差。近年来,研究揭示了Cys2His2锌指基因(CHZFs)和长链非编码rna (lncRNAs)在癌症发展中的关键作用。目前,与Cys2His2 (C2H2)锌指蛋白(ZFPs)相关的lncrna在ccRCC中的预后价值知之甚少。本研究的目的是构建c2h2相关lncrna的预后模型,以帮助临床治疗的选择。方法:从The Cancer Genome Atlas (TCGA)数据库下载rna测序数据及相关临床和预后信息。采用单因素和多因素Cox回归分析鉴定Cys2His2锌指相关长链非编码rna (CHZFLs)并构建预测特征。采用受试者工作特征(ROC)曲线分析验证风险模型。采用Kaplan-Meier法分析两组患者的预后。通过单因素和多因素Cox回归分析评估这些特征的独立预后意义。通过免疫功能和免疫检查点的差异分析证实了CHZFL标记与ccRCC肿瘤免疫之间的关系。结果:构建了5个lncrna (AL117336.2、AC026401.3、AC124854.1、DBH-AS1和LINC02100)的特征。结果显示CHZFLs特征与ccRCC患者的预后有很强的相关性。chzfl的预后特征是ccRCC患者独立的预后因素。预测特征的诊断效能高于单个临床病理变量,其ROC曲线下面积(AUC)为0.775。临床亚组分析结果显示,高危组总生存期(OS)短于低危组。常见的化疗药物,包括长春瑞滨、阿糖胞苷、表柔比星和吉西他滨,在高危人群中引起敏感性增加。此外,单样本基因集富集分析(ssGSEA)显示,ccRCC患者的免疫状态与预测参数有实质性的联系。结论:CHZFL的5个特征可以帮助预测ccRCC患者的预后,并有助于临床选择免疫治疗和化疗方案。
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来源期刊
CiteScore
4.10
自引率
5.00%
发文量
80
期刊介绍: ranslational Andrology and Urology (Print ISSN 2223-4683; Online ISSN 2223-4691; Transl Androl Urol; TAU) is an open access, peer-reviewed, bi-monthly journal (quarterly published from Mar.2012 - Dec. 2014). The main focus of the journal is to describe new findings in the field of translational research of Andrology and Urology, provides current and practical information on basic research and clinical investigations of Andrology and Urology. Specific areas of interest include, but not limited to, molecular study, pathology, biology and technical advances related to andrology and urology. Topics cover range from evaluation, prevention, diagnosis, therapy, prognosis, rehabilitation and future challenges to urology and andrology. Contributions pertinent to urology and andrology are also included from related fields such as public health, basic sciences, education, sociology, and nursing.
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