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.
Abstract
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.
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