A Novel TGF-β Risk Score Predicts the Clinical Outcomes and Tumour Microenvironment Phenotypes in Bladder Cancer

BackgroundThe TGF-beta pathway plays critical roles in numerous malignancies. Nevertheless, its potential role in prognosis prediction and regulating tumour microenvironment (TME) characteristics require further elucidation in bladder cancer (BLCA). MethodsTGF-beta-related genes were comprehensively summarized from several databases. The TCGA-BLCA cohort (training cohort) was downloaded from the Cancer Genome Atlas, and the independent validation cohorts were gathered from Xiangya Hospital (Xinagya cohort) and Gene Expression Omnibus. Initially, we identified differentially expressed TGF-beta genes (DEGs) between cancer and normal tissues. Subsequently, univariate Cox analysis was applied to identify prognostic DEGs, which were further used to develop the TGF-beta risk score by performing LASSO and multivariate Cox analyses. Then, we studied the role of the TGF-beta risk score in predicting prognosis and the TME phenotypes. In addition, the role of the TGF-beta risk score in guiding precision treatments for BLCA has also been assessed. ResultsWe successfully constructed a TGF-beta risk score with an independent prognostic prediction value. A high TGF-beta risk score indicated an inflamed TME, which was supported by the positive relationships between the risk score, enrichment scores of anticancer immunity steps, and the infiltration levels of tumour-infiltrating immune cells. In addition, the risk score positively correlated with the expression of several immune checkpoints and the T cell inflamed score. Consistently, the risk score was positively related to the enrichment scores of most immunotherapy-positive pathways. In addition, the sensitivities of six common chemotherapeutic drugs were positively associated with the risk score. Furthermore, higher risk score indicated higher sensitivity to radiotherapy and EGFR-targeted therapy. On the contrary, patients with low-risk scores were more sensitive to targeted therapies, including the blockade of FGFR3 and WNT-beta-catenin networks. ConclusionsWe first constructed and validated a TGF-beta signature that could predict the prognosis and TME phenotypes for BLCA. More importantly, the TGF-beta risk score could aid in individual precision treatment for BLCA.

Automated summary

In this study, a TGF-beta signature was constructed and validated to predict prognosis and TME phenotypes for BLCA. The TGF-beta risk score could assist in individual precision treatment for BLCA.