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

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.