Identification of key genes and functional coexpression modules in ulcerative colitis by gene datasets analysis

<b><i>Background/Aims</i></b><b><i>:</i></b>Ulcerative colitis is a type of inflammatory bowel disease posing a great threat to the public health worldwide.Previously, gene expression studies of mucosal colonic biopsies have provided some insight into the pathophysiological mechanisms in ulcerative colitis; however, the exact pathogenesis is unclear. This study aimed to identify key genes and pathways associated with ulcerative colitis by bioinformatics analysis.<b><i>Methods</i></b><b><i>:</i></b>Genome-wide gene expression datasets involving ulcerative colitis patients were collected from gene expression omnibus database. To identify key genes, an integrated analysis of gene expression signature was performed by employing robust rank aggregation method. We used weighted gene coexpression network analysis to explore the functional modules involved in ulcerative colitis pathogenesis. Besides, biological process and pathways analysis of co-expression modules were figured out by gene ontology enrichment analysis using metascape.<b><i>Results</i></b><i>:</i>328 ulcerative colitis patients and 138 healthy controls were from fourtreen datasets. MMP1 and AQP8 were two key genes screened from the differentially genes. Seven main functional modules were identified, of which the blue modules included 1718 genes and mainly enriched in extracellular matrix organization, lymphocyte activation, blood vessel morphogenesis, leukocyte migration and inflammatory response,and the salmon module enriched in interferon signaling,defense response to virus and herpes simplex infection. There were also several other meaningful functional modules which were involved in many biological processes.<b><i>Conclusions</i></b><i>:</i>The present study identifies a number of key genes and pathways involved in the progress of ulcerative colitis,which deepens the understanding of the molecular mechanism and provides theoretical foundation for molecular target therapy.<i></i><i></i><br>

<b><i>背景/研究目的</i></b><b><i>：</i></b>溃疡性结肠炎（Ulcerative Colitis, UC）是一类炎症性肠病，对全球公共卫生构成重大威胁。既往针对结肠黏膜活检组织的基因表达研究，已为溃疡性结肠炎的病理生理机制提供了部分见解，但确切的发病机制仍未明确。本研究旨在通过生物信息学分析，筛选与溃疡性结肠炎相关的关键基因及信号通路。
<b><i>研究方法</i></b><b><i>：</i></b>从基因表达综合（Gene Expression Omnibus, GEO）数据库中检索收录溃疡性结肠炎患者的全基因组基因表达数据集。为筛选关键基因，采用稳健秩和聚合（robust rank aggregation）分析法对基因表达特征进行整合分析。此外，通过加权基因共表达网络分析（weighted gene coexpression network analysis, WGCNA）挖掘参与溃疡性结肠炎发病机制的功能模块；利用Metascape平台开展基因本体（Gene Ontology, GO）富集分析，对共表达模块进行生物学过程及通路注释。
<b><i>研究结果</i></b><b><i>：</i></b>本研究纳入来自4项数据集的328例溃疡性结肠炎患者与138例健康对照。从差异表达基因中筛选出MMP1与AQP8这2个关键基因。共鉴定出7个主要功能模块，其中蓝色模块包含1718个基因，主要富集于细胞外基质组织、淋巴细胞活化、血管形态发生、白细胞迁移及炎症反应等生物学过程；鲑鱼模块则富集于干扰素信号通路、病毒防御应答及单纯疱疹病毒感染相关通路。此外还存在多个参与多种生物学过程的其他功能性模块。
<b><i>研究结论</i></b><b><i>：</i></b>本研究筛选出多个参与溃疡性结肠炎发生发展过程的关键基因与信号通路，加深了对其分子机制的理解，可为分子靶向治疗提供理论依据。