Abstract
Background and Objective: Bladder cancer is the most common tumor in the urinary system, with a higher incidence in men than in women and a high recurrence rate. However, the mechanism of recurrence is still unclear, and it is urgent to clarify the pathophysiological mechanism of bladder cancer. To provide theoretical basis for the development of new therapies, investigating the effect of tumor microenvironment on the prognosis of bladder cancer is necessary. Methods: We applied the Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE) algorithm to the downloaded TCGA (The Cancer Genome Atlas) transcriptome data to obtain the immune scores and stromal scores of each sample, and then divided the samples into two groups: high and low immune scores (or high and low stromal scores), and found that some differential genes were associated with poor prognosis of patients. We then performed protein-protein interaction (PPI) network analysis to explore the relationship between these differentially expressed genes. Moreover, we also performed (Gene Ontology) GO and (Kyoto Encyclopedia of Genes and Genomes) KEGG analyses to explore the potential functions of differentially expressed genes. Finally, our results were validated in an independent dataset. Results: We identified 136 tumor microenvironment-related genes associated with poor prognosis of bladder cancer. GO annotation and KEGG pathway enrichment analysis found that these genes are mainly involved in extracellular matrix, Focal adhesion and phosphatidylinositol 3 kinase-protein kinaseB (PI3k-Akt) signaling pathway. Next, PPI network analysis revealed some hub genes including Versican (VCAN), Thrombospondin 1 (THBS1) and Thrombospondin 1 (THBS2). Finally, 27 genes were further verified in the independent data set. Conclusions: We found 27 tumor microenvironment-related genes of bladder cancer, which are associated with poor prognosis of bladder cancer. These genes may inspire researchers to develop new treatments for bladder cancer.
Highlights
Bladder cancer (BLCA) is the most common cancer of the urinary system and is most common in men (Siegel et al, 2018)
Studies have shown that stromal cells in tumor microenvironment, such as fibroblasts, are related to the exocrine phenotype of T cells in bladder cancer (Mariathasan et al, 2018), while the presence of immune cells can mediate the killing of tumor cells through various mechanisms
Based on the ESTIMATE algorithm, the stromal scores range from −3112.294 to 1170.948, and the immune scores range from −2467.750 to 2203.117 (Figures 1A, B)
Summary
Bladder cancer (BLCA) is the most common cancer of the urinary system and is most common in men (Siegel et al, 2018). The tumor microenvironment is composed of cancer cells and non-cancer cell components such as immune cells, stromal cells, endothelial cells, inflammatory cytokines, and extracellular matrix. Studies have shown that stromal cells in tumor microenvironment, such as fibroblasts, are related to the exocrine phenotype of T cells in bladder cancer (Mariathasan et al, 2018), while the presence of immune cells can mediate the killing of tumor cells through various mechanisms. Non-immune cell components in tumor microenvironment affect the treatment response. The treatment effect of bladder cancer changes with the degree of infiltration of stromal cells. Many studies have shown that tumor gene expression profile can quantify the immune activity in tumor microenvironment, such as the infiltration degree of CD8 (+) T cells (Sweis et al, 2016), so the gene expression profile of tumor tissue can reflect the relationship between tumor microenvironment and patient prognosis. To provide theoretical basis for the development of new therapies, investigating the effect of tumor microenvironment on the prognosis of bladder cancer is necessary
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