通过生物信息学分析鉴定参与膀胱癌进展的细胞外基质（ECM）和上皮-间质转化（EMT）相关基因。

Identification of ECM and EMT relevant genes involved in the progression of bladder cancer through bioinformatics analysis.

作者信息

Cao Kai, Shi Honglei, Wu Bin, Lv Zhong, Yang Rong

机构信息

Department of Urology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine Nanjing 210008, Jiangsu, China.

Department of Urology, Wujin Hospital Affiliated with Jiangsu University Changzhou 213164, Jiangsu, China.

出版信息

Am J Clin Exp Urol. 2024 Aug 25;12(4):183-193. doi: 10.62347/XNTC7030. eCollection 2024.

DOI:10.62347/XNTC7030

PMID:39308592

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11411181/

Abstract

BACKGROUND

Bladder cancer (BC) is very common among cancers of urinary system. It was usually categorized into two types: non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). NMIBC and MIBC groupings are heterogeneous and have different characteristics.

OBJECTIVES

The study was aimed to find some hub genes and related signal pathways which might be engaged in the progression of BC and to investigate the relationship with clinical stages and its prognostic significance.

METHODS

GSE37317 datasets were acquired from Gene Expression Omnibus (GEO) database. GEO2R on-line tool was selected to screen the differentially expressed genes (DEGs) of the two different types of BC. Then, Gene Ontology (GO) enrichment and KOBAS-Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of these DEGs were conducted. A protein-protein interaction (PPI) network was employed to help us screen hub genes and find significant modules. Finally, we made analysis of gene expression and survival curve by GEPIA and Kaplan-Meier plotter database.

RESULTS

224 DEGs were screened in total, with 110 showing increased expression and 114 demonstrating decreased expression. GO and KEGG pathway enrichment analysis showed that DEGs were mostly involved in collagen fibril organization, extracellular matrix (ECM) structural constituent, bHLH transcription factor binding, AGE-RAGE signaling pathway and TGF-beta signaling pathway. Only 3 hub genes (DCN, JUN, THBS1) displayed significantly higher expression compared to those in the healthy controls. These hub genes were also strongly related to clinical stages as well as overall survival (OS) of BC patients.

CONCLUSIONS

Taken together, most of hub genes involved in the progression of BC were related to ECM and EMT. In addition, 3 hub genes (DCN, JUN, THBS1) were strongly related with clinical stages and OS of BC patients. This study can enhance our comprehension of the progression of NMIBC and identify novel potential targets for MIBC.

摘要

背景

膀胱癌（BC）在泌尿系统癌症中非常常见。它通常分为两种类型：非肌层浸润性膀胱癌（NMIBC）和肌层浸润性膀胱癌（MIBC）。NMIBC和MIBC分组具有异质性且具有不同特征。

目的

本研究旨在寻找一些可能参与BC进展的枢纽基因和相关信号通路，并研究其与临床分期的关系及其预后意义。

方法

从基因表达综合数据库（GEO）获取GSE37317数据集。选择GEO2R在线工具筛选两种不同类型BC的差异表达基因（DEG）。然后，对这些DEG进行基因本体（GO）富集和京都基因与基因组百科全书（KEGG）通路分析。采用蛋白质-蛋白质相互作用（PPI）网络帮助我们筛选枢纽基因并找到显著模块。最后，通过GEPIA和Kaplan-Meier绘图仪数据库进行基因表达和生存曲线分析。

结果

共筛选出224个DEG，其中110个表达增加，114个表达降低。GO和KEGG通路富集分析表明，DEG主要参与胶原纤维组织、细胞外基质（ECM）结构成分、bHLH转录因子结合、AGE-RAGE信号通路和TGF-β信号通路。与健康对照相比，只有3个枢纽基因（DCN、JUN、THBS1）表达显著更高。这些枢纽基因也与BC患者的临床分期以及总生存期（OS）密切相关。