Identification Of Microenvironment Related Prognostic Genes In Bladder Cancer Based On Gene Expression Profiles

ObjectiveBladder 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.The stromal and immune cells,which constitute the microenvironment of bladder tumor,play a key role in the invasion and metastasis of tumor.However,the current interpretation of transcritpome data of bladder cancer mainly focuses on cancer cells,while ignoring the role of stromal and immune cells in the process of tumor progression.This study investigated the effect of tumor microenvironment on the prognosis of bladder cancer based on transcriptome data from cancer tissues.MethodsThis study applied the ESTIMATE algorithm to the downloaded 426 bladder cancer transcriptome data from TCGA database so as 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 cox proportional hazard regression analysis and Protein-Protein Interaction(PPI)network analysis to explore the relationship between these differentially expressed genes.Moreover,we also performed(Gene Ontology)GO and KEGG(Kyoto Encyclopedia of Genes and Genomes)analyses to explore the potential functions of differentially expressed genes.Finally,this results were validated in an independent dataset.ResultsThis research 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),Thrombospondin 2(THBS2)and AHNAK Nucleoprotein(AHNAK2).Finally,27 genes were further verified in the independent data set and the AHNAK2 gene can be used as an independent prognostic factor.ConclusionThis study found 27 tumor microenvironment-related genes of bladder cancer,which are associated with poor prognosis of bladder cancer.These genes may provide new biomarkers for prognosis of patients.Figure 6 table 3 reference 102...