AUTHOR=Shen Junlin , Du Mingyang , Liang Shuang , Wang Linhui , Bi Jianbin 

TITLE=Construction of a cuproptosis-associated lncRNA prognostic signature for bladder cancer and experimental validation of cuproptosis-related lncRNA UBE2Q1-AS1

JOURNAL=Frontiers in Medicine

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1222543

DOI=10.3389/fmed.2023.1222543

ISSN=2296-858X

ABSTRACT=Copper levels are significantly altered in patients with thyroid, breast, lung, cervical, ovarian, pancreatic, oral, gastric, bladder, and prostate cancers. Outcomes can be predicted by constructing signatures using lncRNA-related genes associated with outcomes. We identified lncRNAs related to outcomes, those differentially expressed in bladder cancer, and cuproptosis-related lncRNAs from TCGA. We identified the intersection to obtain 12 genes and established a prognostic risk signature consisting of eight genes using LASSO-penalized multivariate Cox analysis. We constructed a training set, performed survival analysis on the high-and low-risk groups, and performed validation in the test and full sets. There existed a substantial contrast in the likelihood of survival amongst the cohorts of high and low risk. Univariate survival analysis of the eight genes showed that each gene distinguished between high-and low-risk groups. Sub-group analysis revealed that our risk score differed significantly in tumor stage, age, and gender. An in-depth analysis of the gene mutations associated with tumors was conducted to evaluate the risk of developing cancer. The results indicated a significant difference in the tumor mutation burden (TMB) between the low-and high-risk groups, which had a direct impact on the outcomes. These findings highlight the importance of TMB as a potential prognostic marker in cancer detection and prevention.We analyzed the immune microenvironment and found significant differences in immune function, validation responses, immunotherapy-related positive markers, and critical steps in the tumor immunity cycle between the high-and low-risk groups. We conducted an in-depth study of the immune checkpoints PD-1 and CTLA4 and found that the effect of anti-CTLA4 and PD-1 was higher in the high-risk group than in the low-risk group. Gene analysis of neoadjuvant chemotherapy revealed that the treatment effect in the high-risk group was better than in the low-risk group. We established a signature consisting of eight genes constructed from cuproptosis-related lncRNAs that have potential clinical applications for outcomes prediction, diagnosis, and treatment. This is a provisional file, not the final typeset article 1 UCSC Xena database (https://xena.ucsc.edu/).