Objective  To screen for prognostic methylation-related genes in bladder urothelial carcinoma (BLCA) and explore their value in the prognosis of BLCA.

Methods  Download the sample data of the BLCA project from the TCGA database, obtain the methylation-related genes with a correlation score greater than 5 from the GeneCards database. Prognostic genes were identified using Lasso regression screening. GO and KEGG enrichment analysis were used to explore the functions and pathways involved in prognostic genes, and Cox regression analysis was used to identify genes with potential prognostic value. Receiver operator characteristic (ROC) curve and the area under the curve (AUC) was used to evaluate the prognostic model.

Results  A total of 411 data with clinical samples and 206 methylation-related genes were obtained. 11 methylation-related genes with significant prognostic value were screened out, including VHL, THBS1, SMYD2, RARB, PRMT6, MYC, IGF2, ICMT, EGFR, DLEC1 and CARM1. Enrichment analysis showed that these genes were mainly involved in pathways such as complement and coagulation cascades, neuroactive ligand-receptor interactions, and tyrosine metabolism pathways. The results of the multivariate Cox regression analysis indicate that tumor invasion [HR=2.556, 95%CI(1.190, 5.491)] and high IGF2 expression [HR=3.088, 95%CI(1.348, 7.075)] were associated with poor prognosis in BLCA, whereas high VHL expression [HR=0.358, 95%CI(0.151, 0.845)] was a protective factor for BLCA. The ROC analysis showed that the AUC for overall survival at 1, 3, and 5 years were 0.733, 0.719, and 0.725 respectively, indicating that the prognostic model had good predictive performance.

Conclusion  This study identified 11 methylation-related genes, tumour infiltration, high IGF2 expression, and high VHL expression may be associated with BLCA prognosis.

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