Identification of DNA Replication Stress-Related Genes as Prognostic Biomarkers for Bladder Cancer

Area of Science:

• Oncology
• Genetics
• Bioinformatics

Background:

• Bladder cancer (BLCA) is an aggressive malignancy with a poor prognosis.
• DNA replication stress-related genes (DRSGs) are significant in various cancers and may serve as biomarkers or therapeutic targets in BLCA.

Purpose of the Study:

• To identify prognostic DNA replication stress-related genes (DRSGs) in bladder cancer (BLCA).
• To develop a risk score model for predicting overall survival (OS) in BLCA patients.
• To investigate the functional impact of DRSGs on BLCA cell proliferation and migration.

Main Methods:

• Utilized public databases (TCGA, GEO) and bioinformatics tools to identify DRSGs in BLCA.
• Constructed a prognostic risk score model using univariate Cox and LASSO regression.
• Performed Western blotting, wound healing, Transwell migration, and CCK-8 assays to validate gene expression and functional effects.

Main Results:

• Identified five DRSGs with significant prognostic value in BLCA.
• The constructed risk score model effectively predicted overall survival (OS) in both training and validation cohorts (P < 0.05).
• Functional assays confirmed the role of DRSGs in BLCA cell proliferation and migration, with Gene Set Enrichment Analysis (GSEA) indicating involvement in tumor-related pathways.

Conclusions:

• This study validates the prognostic value of DRSGs in bladder cancer, identifying potential biomarkers and therapeutic targets.
• The findings provide a foundation for further clinical investigation using multicenter cohorts and animal models to confirm relevance.