Identification and validation of the nicotine metabolism-related signature of bladder cancer by bioinformatics and machine learning

作者：Yating Zhan, Min Weng, Yangyang Guo, Dingfeng Lv, Feng Zhao, Zejun Yan, Junhui Jiang, Yanyi Xiao, Lili Yao · 发表于：Frontiers in Immunology · 年份：2024 · DOI：10.3389/fimmu.2024.1465638 · 被引用次数：5 · 研究领域：Nicotinic Acetylcholine Receptors Study、Cancer, Stress, Anesthesia, and Immune Response、Tryptophan and brain disorders

Background: Several studies indicate that smoking is one of the major risk factors for bladder cancer. Nicotine and its metabolites, the main components of tobacco, have been found to be strongly linked to the occurrence and progression of bladder cancer. However, the function of nicotine metabolism-related genes (NRGs) in bladder urothelial carcinoma (BLCA) are still unclear. Methods: NRGs were collected from MSigDB to identify the clusters associated with nicotine metabolism. Prognostic differentially expressed genes (DEGs) were filtered via differentially expression analysis and univariate Cox regression analysis. Integrative machine learning combination based on 10 machine learning algorithms was used for the construction of robust signature. Subsequently, the clinical application of signature in terms of prognosis, tumor microenvironment (TME) as well as immunotherapy was comprehensively evaluated. Finally, the biology function of the signature gene was further verified via CCK-8, transwell migration and colony formation. Results: Three clusters associated with nicotine metabolism were discovered with distinct prognosis and immunological patterns. A four gene-signature was developed by random survival forest (RSF) method with highest average Harrell's concordance index (C-index) of 0.763. The signature exhibited a reliable and accurate performance in prognostic prediction across TCGA-train, TCGA-test and GSE32894 cohorts. Furthermore, the signature showed highly correlat...