Tian Ting, Shen Cheng, Zapała Łukasz, Fang Xingxing, Zheng Bing
Operating Room Nursing, The Second Affiliated Hospital of Nantong University, Nantong, China.
Department of Urology, The Second Affiliated Hospital of Nantong University, Nantong, China.
Transl Androl Urol. 2025 Feb 28;14(2):412-431. doi: 10.21037/tau-2024-769. Epub 2025 Feb 25.
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.
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.
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.
The five CHZFL signature can help predict the prognosis of ccRCC patients, and assist in selecting immunotherapy and chemotherapy regimens in clinical practice.
透明细胞肾细胞癌（ccRCC）是肾细胞癌的主要组成部分，晚期ccRCC往往预示着预后不良。近年来，研究揭示了半胱氨酸2-组氨酸2锌指基因（CHZFs）和长链非编码RNA（lncRNAs）在癌症发生发展中的关键作用。目前，关于与半胱氨酸2-组氨酸2（C2H2）锌指蛋白（ZFPs）相关的lncRNAs在ccRCC中的预后价值知之甚少。本研究的目的是构建一个与C2H2相关的lncRNAs预后模型，以辅助临床治疗方案的选择。
从癌症基因组图谱（TCGA）数据库下载RNA测序数据以及相关的临床和预后信息。进行单因素和多因素Cox回归分析，以鉴定与半胱氨酸2-组氨酸2锌指相关的长链非编码RNA（CHZFLs）并建立预测特征。进行受试者工作特征（ROC）曲线分析以验证风险模型。使用Kaplan-Meier方法分析各组的预后。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CHZFL特征与ccRCC肿瘤免疫之间的关系。
构建了一个由五个lncRNAs（AL117336.2、AC026401.3、AC124854.1、DBH-AS1和LINC02100）组成的特征。结果显示CHZFLs特征与ccRCC患者的预后密切相关。CHZFLs的预后特征是ccRCC患者的独立预后因素。预测特征的诊断效能高于个体临床病理变量，其曲线下面积（AUC）为0.775。临床亚组分析结果显示，高危组的总生存期（OS）短于低危组。包括长春瑞滨、阿糖胞苷、表柔比星和吉西他滨在内的常用化疗药物在高危组中引起更高的敏感性。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密切相关。
五个CHZFL特征有助于预测ccRCC患者的预后，并在临床实践中辅助选择免疫治疗和化疗方案。
