Construction and experimental validation of a B cell-related gene signature to predict the prognosis and immunotherapeutic sensitivity in bladder cancer

Abstract

Background: B cells are essential components of tumor microenvironment and exert important functions in anti-tumor immune response. However, the prognosis value of B cell-related genes in bladder cancer (BLCA) remains obscure. Materials and Methods: The infiltrating levels of B cells were measured via the CD20 staining in the local samples and the computational biology analyses in the TCGA-BLCA cohort. The single-cell RNA sequencing analysis, gene-pair strategy, LASSO regression, random forest, and Cox regression were used for B cell-related signature construction. TCGA-BLCA cohort was chosen as the training cohort, and three independent cohorts from GEO and the local cohort were used for external validation. 326 B cells were adopted to explore the association between the model and B cells' biological processes. TIDE algorithm and two BLCA cohorts receiving anti-PD1/PDL1 treatment were utilized to detect its predictive ability to the immunotherapeutic response. Results: High infiltration levels of B cells heralded favorable prognosis, both in the TCGA-BLCA cohort and the local cohort (all P < 0.05). A 5-gene-pair model was established and served as a significant prognosis predictor across multiple cohorts (pooled hazard ratio = 2.79, 95% confidence interval = 2.22-3.49). The model could evaluate the prognosis effectively in 21 of 33 cancer types (P < 0.05). The signature was negatively associated with B cells' activation, proliferation, and infiltrating levels, and could serve as a potential predictor of immunotherapeutic outcomes. Conclusions: A B cell-related gene signature was constructed to predict the prognosis and immunotherapeutic sensitivity in BLCA, helping to guide the personalized treatment.

Investigating the impact of regulatory B cells and regulatory B cell-related genes on bladder cancer progression and immunotherapeutic sensitivity

“…We obtained the established prognosis signatures linked to B cell profiles in BLCA from published literature (Table S11 ) [ 26 – 29 ]. Risk scores for the TCGA-BLCA subjects were computed using the provided formula (Table S12 ).…”

“…In this study, we have successfully established a prognostic and immunotherapeutic efficacy indicator in the form of a Breg-related gene signature, which was rigorously validated through meta-analysis and in vitro experiments. Importantly, we compared the prognosis predictive ability of the Breg-related gene signature with the established risk signature associated with B cells’ profiles [ 26 – 29 ], and the results suggested that BREGRS was of the strongest predictive ability for OS in the TCGA-BLCA cohort. Besides, BREGRS emerged as a significant predictor for immunotherapeutic sensitivity within immunotherapeutic cohorts.…”