Comprehensive analysis of cuproptosis-related long noncoding RNA immune infiltration and prediction of prognosis in patients with bladder cancer

Abstract

Background: Bladder cancer (BCa), among the world’s most common malignant tumors in the urinary system, has a high morbidity and mortality. Though cuproptosis is a new type of cell death mediated by lipoylated tricarboxylic acid (TCA) cycle proteins, the role of cuproptosis-related long noncoding RNAs (crlncRNAs) in bladder tumors awaits further elucidation. In this paper, we tried to explore how important crlncRNAs are for BCa. Methods: The crlncRNAs were first obtained through Pearson correlation analysis of the RNA-seq data and corresponding clinical data downloaded from The Cancer Genome Atlas (TCGA). Then, three lncRNAs were acquired by Cox regression and Lasso regression to build a prognostic model of crlncRNAs for verification. In the meantime, clinicopathological correlation analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, principal component analysis (PCA), immunoassay, and half-maximal inhibitory concentration prediction (IC50) were carried out. Then, an entire tumor was classified into two clusters by crlncRNA expression to further discuss the differences in prognosis, immune status and drug susceptibility among different subgroups. Results: We obtained a total of 152 crlncRNAs and built a risk model for screened crlncRNAs. We validated the model and found that calibration charts feature a high consistency in verifying nomogram prediction. Receiver operating characteristic (ROC) curve and univariate and multivariate Cox regression suggested that this model can be applied as an independent prognostic factor of bladder cancer due to its high accuracy. According to KEGG analysis, high-risk groups were enriched in cancer and immune-related pathways. During tumor immunoassay, noticeable differences were observed in both immune infiltration and checkpoints between high- and low-risk patients. Of the two subgroups divided among patients by consensus clustering, cluster 2 had a better prognosis, whereas cluster 1 had higher immunoreactivity scores, more immune cell infiltrations and immune checkpoint expressions, and different sensitivities to drugs. Conclusion: The research findings demonstrate that crlncRNAs can be used to predict the prognosis and immune microenvironment of patients suffering from BCa, and differentiate between BCa subgroups to improve the individual therapy of BCa.