A novel T-cell proliferation-associated regulator signature pre-operatively predicted the prognostic of bladder cancer

Abstract

Background: Bladder cancer (BCa) is a remarkably malignant and heterogeneous neoplastic disease, and its prognosis prediction is still challenging. Even with the mounting researches on the mechanisms of tumor immunotherapy, the prognostic value of T-cell proliferation regulators in bladder cancer remains elusive.

Methods: Herein, we collected mRNA expression profiles and relevant clinical information of bladder cancer sufferers from a publicly available data base. Then, the LASSO Cox regression model was utilized to establish a multi-gene signature for the TCGA cohort to predict the prognosis and staging of bladder cancer. Eventually, the predictive power of the model was validated by randomized grouping.

Results: The outcomes revealed that most genes related to T-cell proliferation in the TCGA cohort exhibited different expressions between BCa cells and neighboring healthy tissues. Univariable Cox regressive analyses showed that four DEGs were related to OS in bladder cancer patients (p<0.05). We constructed a histogram containing four clinical characteristics and separated sufferers into high- and low-risk groups. High-risk sufferers had remarkably lower OS compared with low-risk sufferers (P<0.001). Eventually, the predictive power of the signature was verified by ROC curve analyses, and similar results were obtained in the validation cohort. Functional analyses were also completed, which showed the enrichment of immune-related pathways and different immune status in the two groups. Moreover, by single-cell sequencing, our team verified that CXCL12, a T-lymphocyte proliferation regulator, influenced bladder oncogenesis and progression by depleting T-lymphocyte proliferation in the tumor microenvironment, thus promoting tumor immune evasion.

Conclusion: This study establishes a novel T cell proliferation-associated regulator signature which can be used for the prognostic prediction of bladder cancer. The outcomes herein facilitate the studies on T-cell proliferation and its immune micro-environment to ameliorate prognoses and immunotherapeutic responses.

Keywords: T-cell proliferation regulator; bladder cancer; predictive gene signature; prognostic; single cell sequencing.