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

Abstract

BackgroundBladder 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.MethodsHerein, 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.ResultsThe 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.ConclusionThis 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.

Subtype classification based on t cell proliferation-related regulator genes and risk model for predicting outcomes of lung adenocarcinoma

“…In the original study, most of these TPRGs have been demonstrated to increase the proliferation cancer analysis shows that oncogene CDK1 is an immunological and prognostic biomarker, which may influence tumor immunity mainly by mediating the migration of immune cells to TME, and is positively associated with tumor mutational burden and microsatellite instability (54). CXCL12 is highly enriched in fibroblasts (16). Fibroblasts in bladder cancer parietal tissue promote bladder carcinogenesis and progression by paracrine secretions of CXCL12 into TME to interact specifically with CXCR4 receptors (a specific receptor for CXCL12, expressed in T cells and macrophages in tumor tissues) and promote the proliferation of depleted T cells in cancer tissues (16).…”

“…CXCL12 is highly enriched in fibroblasts (16). Fibroblasts in bladder cancer parietal tissue promote bladder carcinogenesis and progression by paracrine secretions of CXCL12 into TME to interact specifically with CXCR4 receptors (a specific receptor for CXCL12, expressed in T cells and macrophages in tumor tissues) and promote the proliferation of depleted T cells in cancer tissues (16). Those subtypes divided by the risk model showed remarkably differences in biology function and pathway, mutation status, immunity and drug susceptibility.…”

“…We obtained two external microarray datasets GSE31210 (including 246 LUAD patients and survival imformation) and GSE68465 (including 442 LUAD patients and survival imformation) from the GEO database. A total of 35 TPRGs were extracted from the published studies ( 16 ).…”

“…However, abundant evidence argues that T cell proliferation is imperfect for measuring tumorreactivity and outcomes (8,(10)(11)(12)(13)(14)(15). Recently, Mateusz Legut et al, for the first time, defined T cell proliferation-related regulator genes (TPRGs) (16,17). In that article, many positive TPRGs that enhance T cell functions are identified (17).…”

Bioinformatics identification of a T‐cell‐related signature for predicting prognosis and drug sensitivity in hepatocellular carcinoma

“…Recently, T‐cell‐based anticancer immunotherapies have brought substantial benefits to many patients, and the clinical effectiveness changes remarkably across tumour types [ 40 ]. However, the crosstalk between the TME and tumour could functionally reprogramme and sculpt the TME.…”