Construction and Validation of a Ubiquitination-Related Gene Signature Based on WGCNA and Single-cell RNA Sequencing in Bladder Cancer.

BACKGROUND: The potential pathogenesis and reliable biomarkers of Bladder cancer (BC) remain to be explored. Ubiquitination plays a crucial role in BC progression, warranting the necessity to develop prognostic gene signatures. METHODS: By integrating weighted gene co-expression network analysis (WGCNA) and single-cell RNA sequencing (scRNA-seq), we identified the genes related to the single-- cell ubiquitination activity. A prognostic gene signature was established using univariate Cox analysis, LASSO analysis, and multivariate Cox analysis. BC patients were stratified into high-risk and low-risk groups according to the median risk score. The nomogram was constructed and validated. Potential biological processes of common ubiquitination-related genes anisk groups were explored. The immune infiltration, immunotherapy response, and drug sensitivity were evaluated. RESULTS: A six-gene signature comprising CAPG, EMP3, GMFG, HLA-B, ID1, and TNFRSF12A stratified patients into high-risk and low-risk groups with significantly different overall survival. In the training group, the area under the curve was 0.695 at 1 year, 0.725 at 3 years, and 0.739 at 5 years. The high-risk group generally showed worse overall survival compared to the low-risk group. The nomogram model showed satisfactory predictive performance. Significant differences in immune cell proportions were observed in different risk groups. The low-risk group exhibited higher Immune scores and Stromal scores and showed better survival outcomes following PD-L1 immunotherapy. Doxorubicin, Gemcitabine, Methotrexate, and Vinblastine exhibited significantly lower IC50 values in the low-risk group. CONCLUSION: The six-gene ubiquitination-related signature may provide a valuable reference for potential therapeutic targets and prognosis of BC. However, prospective and experimental validation is still required.