Abstract
Bladder cancer (BC) is one of the top ten most common cancer types globally, accounting for approximately 7% of all male malignancies. In the last few decades, cancer research has focused on identifying oncogenes and tumor suppressors. Recent studies have revealed that the interplay between tumor cells and the tumor microenvironment (TME) plays an important role in the initiation and development of cancer. However, the current knowledge regarding its effect on BC is scarce. This study aims to explore how the TME influences the development of BC. We focused on immune and stromal components, which represent the major components of TME. We found that the proportion of immune and stromal components within the TME was associated with the prognosis of BC. Furthermore, based on the scores of immune and stromal components, 811 TME-related differentially expressed genes were identified. Three subclasses with distinct biological features were divided based on these TME-genes. Finally, five prognostic genes were identified and used to develop a prognostic prediction model for BC patients based on TME-related genes. Additionally, we validated the prognostic value of the five-gene model using three independent cohorts. By further analyzing features based on the five-gene signature, higher CD8+ T cells, higher tumor mutational burden, and higher chemosensitivity were found in the low-risk group, which presented a better prognosis. In conclusion, our exploration comprehensively analyzed the TME and identified TME-related prognostic genes for BC, providing new insights into potential therapeutic targets.
Highlights
Bladder cancer (BC) is a highly prevalent disease with an incidence of approximately 7% among all male malignancies and is the eighth most common cause of mortality [1]
To explore the correlation between the estimated proportion of immune and stromal components and the survival rate of BC patients, Kaplan–Meier survival analysis was performed for ImmuneScore, StromalScore, and ESTIMATEScore, respectively [16]
ImmuneScore was not significantly correlated with the overall survival rate, StromalScore and ESTIMATEScore displayed a significant negative correlation with the overall survival (Log Rank test, p
Summary
Bladder cancer (BC) is a highly prevalent disease with an incidence of approximately 7% among all male malignancies and is the eighth most common cause of mortality [1]. The incidence rate of BC has been decreasing, its death rate has not substantially reduced [2]. Tumor progression is a complicated process in which complex interactions occur between the tumor and the surrounding microenvironment. The surrounding microenvironment of tumor cells is referred to as the tumor microenvironment (TME), which includes immune cells, fibroblasts, and nearby stromal tissues [3, 4]. The two major components of the TME are resident stromal cells and recruited immune cells [5, 6]. Studying the heterogeneous components of the TME and their complex interactions is necessary to identify novel therapeutic targets
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