Gastroenterology Department, the First Hospital of China Medical University, No.155 North Nanjing Street, Heping District, Shenyang, Liaoning, China.
The 3rd Clinical Department of China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, China.
Medicine (Baltimore). 2022 Jun 24;101(25):e29379. doi: 10.1097/MD.0000000000029379.
This study aimed to explore aberrantly methylated-differentially expressed genes and related pathways in cholangiocarcinoma (CCA).The mRNA expression data (GSE26566) and methylation profiling data (GSE44965) were collected from the Gene Expression Omnibus (GEO) Datasets. Differentially expressed genes and differentially methylated genes were identified using GEO2R. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using clusterprofiler in R. MCODE clustering tool was used to screen modules of the protein-protein interaction network in Cytoscape. Related pathways of hub gene by using gene set enrichment analysis.Eighty-one hypermethylated, lowly expressed genes (Hyper-LGs) and 76 hypomethylated, highly expressed genes (Hypo-HGs) were identified in this study. Hyper-LGs were enriched in ion channel binding and transcription factor activity, which was associated with Mineral absorption and Cell adhesion molecules. Hypo-HGs were enriched in cysteine-type endopeptidase activity, which was associated with Sphingolipid signaling pathway and T cell receptor signaling pathway. Based on protein-protein interaction networks, MYC and VWF were identified as hub genes for Hyper-LGs, and no hub genes for Hypo-HGs.This study found methylated-differentially expressed genes and signaling pathways that are connected with the CCA by using a series of bioinformatics databases and tools. MYC and VWF act as hub genes of CCA, which can be used as biomarkers based on aberrant methylation for the accurate diagnosis and treatment of CCA.
本研究旨在探索胆管癌（CCA）中异常甲基化的差异表达基因和相关通路。从基因表达综合数据库（GEO）数据集收集了 mRNA 表达数据（GSE26566）和甲基化谱数据（GSE44965）。使用 GEO2R 鉴定差异表达基因和差异甲基化基因。使用 R 中的 clusterprofiler 进行基因本体论分析和京都基因与基因组百科全书通路富集分析。使用 Cytoscape 中的 MCODE 聚类工具筛选蛋白质-蛋白质相互作用网络的模块。使用基因集富集分析研究与枢纽基因相关的通路。本研究鉴定了 81 个高甲基化、低表达基因（Hyper-LGs）和 76 个低甲基化、高表达基因（Hypo-HGs）。Hyper-LGs 富集于离子通道结合和转录因子活性，与矿物质吸收和细胞粘附分子有关。Hypo-HGs 富集于半胱氨酸内肽酶活性，与鞘脂信号通路和 T 细胞受体信号通路有关。基于蛋白质-蛋白质相互作用网络，MYC 和 VWF 被鉴定为 Hyper-LGs 的枢纽基因，而 Hypo-HGs 没有枢纽基因。本研究通过一系列生物信息学数据库和工具，发现了与 CCA 相关的甲基化差异表达基因和信号通路。MYC 和 VWF 作为 CCA 的枢纽基因，可作为基于异常甲基化的标志物，用于 CCA 的准确诊断和治疗。
