Comprehensive Exploration of Tumor Microenvironment Modulation Based on the ESTIMATE Algorithm in Bladder Urothelial Carcinoma Microenvironment.

Ji Chen,Kai Zhu,Yeping Li,Boyu Lv,Yan Jin,Bo Chen,Rongrong Zhang,Changyong Lin,Yating Zhan,Jianjian Zheng

doi:10.3389/fonc.2022.724261

Abstract

Recently, the tumor microenvironment (TME) has been reported to be closely related to the tumor initiation, progression, and prognosis. Bladder urothelial carcinoma (BLCA), one of the most common subtypes of bladder cancer worldwide, has been associated with increased morbidity and mortality in the past decade. However, whether the TME status of BLCA contributes to the prediction of BLCA prognosis still remains uncertain. In this study, the ESTIMATE algorithms were used to estimate the division of immune and stromal components in 406 BLCA samples downloaded from The Cancer Genome Atlas database (TCGA). Based on the comparison between ESTIMATE scores, the differentially expressed genes (DEGs) were selected. Using the univariate Cox regression analysis, prognosis-related DEGs were further identified (p < 0.05). The LASSO regression analysis was then used to screen 11 genes that were highly related to the TME of BLCA to generate a novel prognostic gene signature. The following survival analyses showed that this signature could effectively predict the prognosis of BLCA. The clinical value of this signature was further verified in an external cohort obtained from the First Affiliated Hospital of Wenzhou Medical University (n = 120). Based on the stage-correlation analysis and differential expression analysis, IGF1 and MMP9 were identified as the hub genes in the signature. Additionally, using CIBERSORT algorithms, we found that both IGF1 and MMP9 were significantly associated with immune infiltration. Collectively, a novel TME-related prognostic signature contributes to accurately predict the prognosis of BLCA.

Highlights

Bladder urothelial carcinoma (BLCA), one of the most common subtypes of bladder cancer (BC) worldwide, has been associated with increased morbidity and mortality in the past decade [1, 2]
Using the ESTIMATE algorithm, it was found that the ESTIMATE, the stromal, and the immune scores were significantly associated with gender and grade, especially for the T2 and T3 histologically graded disease (Figures 2A–I)
As shown in the Venn diagram, the common immune cells were selected by the differential analyses and immune cell correlation analyses (Figures 12C, 13C). All these results suggest that IGF1 and MMP9 are closely related to immune infiltrates and may be involved in the immune activity of tumor microenvironment (TME) in BLCA

Summary

Introduction

Bladder urothelial carcinoma (BLCA), one of the most common subtypes of bladder cancer (BC) worldwide, has been associated with increased morbidity and mortality in the past decade [1, 2]. BLCA is the seventh most common cause of cancer-related mortality in the world. BLCA could be categorized into two distinctive types: muscle-invasive bladder cancer (MIBC) and nonmuscle-invasive bladder cancer (NMIBC), of which 25% represents MIBC and 75% represents NMIBC [3]. Patients with NMIBC have a 50%–70% rate of relapse, with a 5-year survival rate >90%. After progressing to MIBC, the 5year survival rate will drop to

Methods

Results

Conclusion