Matrix Metalloproteinase-9 is associated with tumor microenvironment remodeling of bladder cancer.

Abstract

Tumor microenvironment (TME) takes an essential part in the bladder cancer progression, which is associated with intercellular cross-talk between stroma cells and cancer. We aimed use bioinformatics tools to analyze tumor microenvironment remodeling in bladder cancer. CIBERSORT and ESTIMATE are bioinformatics tools based on deconvolution for calculating proportions of tumor-infiltrating immune cells and stromal components in TME. We utilized these two algorithms to analyze the immune components of 433 bladder cancer cases from The Cancer Genome Atlas database, aiming to compensate for the current lack of large-sample single-cell information. Then we used Cox regression to analyze the prognostic value of differentially expressed genes, and the protein-protein interaction network was constructed. Matrix Metalloproteinase-9 (MMP9) was identified as a predictive biomarker related to immune microenvironment. Using Gene Set Enrichment Analysis, the genes from the group with high MMP9 expression gathered in items related to immune diseases, and genes in the group with low MMP9 expression were negatively associated with valine, leucine and isoleucine degradation and glycosylphosphatidylinositol anchor biosynthesis. MMP9 expression and presence of macrophages M0 were positively correlated, while naïve B cells, activated dendritic cells, monocytes and plasma cells were negatively correlated. The results were confirmed by brightfield and multiplex fluorescence immunohistochemistry using stained bladder cancer and normal tissue.