Extracellular matrix-related genes play an important role in the progression of NMIBC to MIBC: a bioinformatics analysis study.

Heng Zhang,Ling-Yue An,Ye Tian,Yong Ban,Gang Shan,Jukun Song,Guang-Heng Luo

doi:10.1042/bsr20194192

Abstract

Bladder cancer is the 11th most common cancer in the world. Bladder cancer can be roughly divided into muscle invasive bladder cancer (MIBC) and non-muscle invasive bladder cancer (NMIBC). The aim of the present study was to identify the key genes and pathways associated with the progression of NMIBC to MIBC and to further analyze its molecular mechanism and prognostic significance. We analyzed microarray data of NMIBC and MIBC gene expression datasets (GSE31684) listed in the Gene Expression Omnibus (GEO) database. After the dataset was analyzed using R software, differentially expressed genes (DEGs) of NMIBC and MIBC were identified. These DEGs were analyzed using Gene Ontology (GO) enrichment, KOBAS-Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein–protein interaction (PPI) analysis. The effect of these hub genes on the survival of bladder cancer patients was analyzed in The Cancer Genome Atlas (TCGA) database. A total of 389 DEGs were obtained, of which 270 were up-regulated and 119 down-regulated. GO and KEGG pathway enrichment analysis revealed that DEGs were mainly involved in the pathway of protein digestion and absorption, extracellular matrix (ECM) receiver interaction, phantom, toll-like receptor (TLR) signaling pathway, focal adhesion, NF-κB signaling pathway, PI3K/Akt signaling pathway, and other signaling pathways. Top five hub genes COL1A2, COL3A1, COL5A1, POSTN, and COL12A1 may be involved in the development of MIBC. These results may provide us with a further understanding of the occurrence and development of MIBC, as well as new targets for the diagnosis and treatment of MIBC in the future.

Highlights

Bladder cancer is the 11th most common cancer in the world, causing 3.2 deaths per 100000 males and 0.9 deaths per 100000 females every year [1]
Using the online analytical tool of Database for Annotation (DAVID) to annotate the differentially expressed gene (DEG) obtained from microarray data integration analysis, the Gene Ontology (GO) function of the DEGs was enriched with a P-value
In GO enrichment analysis, DEGs were divided into three parts: biological process (BP), molecular function (MF), and cell component (CC)

Summary

Introduction

Bladder cancer is the 11th most common cancer in the world, causing 3.2 deaths per 100000 males and 0.9 deaths per 100000 females every year [1]. Bladder cancer can be roughly divided into muscle invasive bladder cancer (MIBC) and non-muscle invasive bladder cancer (NMIBC) depending on whether it infiltrates the bladder muscle layer or not. 75% of bladder cancer patients have NMIBC, which has a better prognosis than MIBC [2]. The treatment for NMIBC is a transurethral resection of the bladder tumor (TURBT) plus bladder drug perfusion, but the first choice for MIBC is radical cystectomy (RC) [3]. It is apparent that muscle invasion in bladder cancer patients has an important impact on determining the appropriate treatment plan and prognosis. There are some theories about the molecular mechanisms involved in NMIBC progression, including oncogene activation [4], immune regulation [5], and extracellular matrix (ECM) alterations [6,7]

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