Identification of cuproptosis-related long non-coding RNA and construction of a novel prognostic signature for bladder cancer: An observational study

Abstract

Bladder Urothelial Carcinoma (BLCA), a prevalent and lethal cancer, lacks understanding regarding the roles and prognostic value of cuproptosis-related lncRNAs (CRLs), a novel form of cell death induced by copper. We collected RNA-seq data, clinical information, and prognostic data for 414 BLCA samples and 19 matched controls from The Cancer Genome Atlas. Using multivariate and univariate Cox regression analyses, we identified CRLs to create a prognostic signature. Patients were then divided into low- and high-risk groups based on their risk scores. We analyzed overall survival using the Kaplan–Meier method, evaluated stromal and immune scores, and explored functional differences between these risk groups with gene set enrichment analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were also conducted to understand the links between CRLs and BLCA development. We developed a prognostic signature using 4 independent CRLs: RC3H1-IT1, SPAG5-AS1, FAM13A-AS1, and GNG12-AS1. This signature independently predicted the prognosis of BLCA patients. High-risk patients had worse outcomes, with gene set enrichment analysis revealing enrichment in tumor- and immune-related pathways in the high-risk group. Notably, high-risk patients exhibited enhanced responses to immunotherapy and conventional chemotherapy drugs like sunitinib, paclitaxel, and gemcitabine. The independent prognostic signature variables RC3H1-IT1, SPAG5-AS1, FAM13A-AS1, and GNG12-AS1 predicted the prognoses of BLCA patients and provided a basis for the study of the mechanism of CRLs in BLCA development and progression, and the guidance of clinical treatments for patients with BLCA.