Sang Liang, Yu Zhanwu, Wang Ang, Li Hao, Dai Xiantong, Sun Liping, Liu Hongxu, Yuan Yuan
Cancer Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang 110001, China; Ultrasound Department, the First Hospital of China Medical University, Shenyang 110001, China.
Department of Thoracic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No. 44 Xiaoheyan Road, Shenyang, Liaoning 110042, China.
Pathol Res Pract. 2020 Sep;216(9):153050. doi: 10.1016/j.prp.2020.153050. Epub 2020 Jun 10.
Methylation, as an epigenetic modification, can affect gene expression and play a role in the occurrence and development of cancer. This research is devoted to discover methylated-differentially expressed genes (MDEGs) in esophageal squamous cell carcinoma (ESCC) and explore special associated pathways. We downloaded GSE51287 methylation profiles and GSE26886 expression profiles from GEO DataSets, and performed a comprehensive bioinformatics analysis. Totally, 19 hypermethylated, lowly expressed genes (Hyper-LGs) were identified, and involved in regulation of cell proliferation, phosphorus metabolic process and protein kinase activity. Meanwhile, 17 hypomethylated, highly expressed genes (Hypo-HGs) were participated in collagen catabolic process, metallopeptidase and cytokine activity. Pathway analysis determined that Hyper-LGs were enriched in arachidonic acid metabolism pathway, while Hypo-HGs were primarily associated with the cytokine-cytokine receptor interaction pathway. IL 6, MMP3, MMP9, SPP1 were identified as hub genes based on the PPI network that combined 7 ranked methods included in cytoHubba, and verification was performed in human tissues. Our integrated analysis identified many novel genetic lesions in ESCC and provides a crucial molecular foundation to improve our understanding of ESCC. Hub genes, including IL 6, MMP3, MMP9 and SPP1, could be considered for use as aberrant methylation-based biomarkers to facilitate the accurate diagnosis and therapy of ESCC.
甲基化作为一种表观遗传修饰，可影响基因表达，并在癌症的发生和发展中发挥作用。本研究致力于发现食管鳞状细胞癌（ESCC）中的甲基化差异表达基因（MDEG），并探索其特殊相关途径。我们从GEO数据集下载了GSE51287甲基化谱和GSE26886表达谱，并进行了全面的生物信息学分析。共鉴定出19个高甲基化、低表达基因（Hyper-LG），它们参与细胞增殖调控、磷代谢过程和蛋白激酶活性。同时，17个低甲基化、高表达基因（Hypo-HG）参与胶原分解代谢过程、金属肽酶和细胞因子活性。通路分析确定Hyper-LG在花生四烯酸代谢通路中富集，而Hypo-HG主要与细胞因子-细胞因子受体相互作用通路相关。基于cytoHubba中包含的7种排序方法组合的PPI网络，将IL-6、MMP3、MMP9、SPP1鉴定为枢纽基因，并在人体组织中进行了验证。我们的综合分析在ESCC中发现了许多新的基因损伤，为增进我们对ESCC的理解提供了关键的分子基础。包括IL-6、MMP3、MMP9和SPP1在内的枢纽基因可被视为基于异常甲基化的生物标志物，以促进ESCC的准确诊断和治疗。
