Alternative splicing event associated with immunological features in bladder cancer

Area of Science:

• Oncology
• Molecular Biology
• Bioinformatics

Background:

• Bladder cancer (BLCA) is a prevalent urinary tumor with limited therapeutic options.
• Alternative splicing (AS) plays a crucial role in cancer development and the tumor immune microenvironment.
• A comprehensive analysis of AS in relation to BLCA prognosis and immunology is currently lacking.

Purpose of the Study:

• To investigate the prognostic and immunological roles of alternative splicing events in bladder cancer.
• To identify novel AS events as potential biomarkers for BLCA.
• To develop a risk score model based on prognostic AS events for predicting patient outcomes and immune status.

Main Methods:

• Downloaded RNA-Seq data and clinical information from The Cancer Genome Atlas (TCGA) database.
• Acquired AS events from TCGA Splice-seq.
• Utilized univariate analysis and LASSO regression to identify prognostic AS events and construct a risk score model.
• Performed Kaplan-Meier analysis, ROC curve analysis, ssGSEA, CIBERSORT, and TIMER database analysis to evaluate the model and gene expression.
• Constructed a regulatory network of AS and splicing factors using Cytoscape.

Main Results:

• Identified eight prognostic AS events (e.g., C19orf57|47943|ES, ANK3|11845|AP, TRMU|62711|AA) and developed a risk score model.
• The high-risk group exhibited a significantly worse prognosis (Kaplan-Meier analysis).
• The risk score model demonstrated good predictive performance (AUCs for 1, 3, 5 years: 0.698, 0.742, 0.772).
• The gene TRMU, associated with AS, was differentially expressed and significantly correlated with immune microenvironment components, including immune cells and checkpoints.
• Established a regulatory network between AS events and splicing factors.

Conclusions:

• Alternative splicing events serve as powerful biomarkers for predicting prognosis and immune status in bladder cancer.
• The developed risk score model effectively predicts BLCA patient outcomes and immune characteristics.
• Identified AS events and related genes, such as TRMU, represent potential therapeutic targets for bladder cancer.