KRT15、INHBA、MATN3 和 AGT 在胃癌中存在异常甲基化和差异表达，并与预后相关。
KRT15, INHBA, MATN3, and AGT are aberrantly methylated and differentially expressed in gastric cancer and associated with prognosis.
机构信息
Department of Gastroenterological Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
Department of Gastroenterological Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
出版信息
Pathol Res Pract. 2019 May;215(5):893-899. doi: 10.1016/j.prp.2019.01.034. Epub 2019 Jan 28.
AIM
The present study aims to identify aberrantly methylated and differentially expressed genes (DEGs) in gastric cancer (GC) and explore their potential role in the carcinogenesis and development of GC.
METHODS
The original RNA-Seq, clinical information and Illumina Human Methylation 27 Chip data associated with GC were downloaded from The Cancer Genome Atlas (TCGA) database using the gdc-client tool. The DEGs and aberrantly methylated genes (AMGs) were screened with edgeR and limma package in R, respectively. The cut-off criteria for DEG identification were P < 0.05 and fold change (FC) >2.0, and for AMG identification were P < 0.05 and |t|>2.0. Genes which were both DEGs and AMGs were considered to be regulated by aberrant DNA methylation in GC. The common genes were used for further functional enrichment analysis in the categories of cellular component, molecular function, biological process and biological pathway.
RESULTS
In total 465 genes including 336 down-regulated genes with hyper-methylation (DGs-Hyper) and 129 up-regulated genes with hypo-methylation (UGs-Hypo) were identified. Cellular component analysis showed that these genes were mainly expressed in the cytoplasm and plasma membrane. Molecular function and biological process analysis indicated that the genes primarily participate in cell communication, signal transduction, cell growth/maintenance and function as transcription factors, receptor, cell adhesion molecules, and transmembrane receptor protein tyrosine kinases. Biological pathway analysis revealed that the genes are involved in some crucial pathways including epithelial-to-mesenchymal transition, IL3-mediated signaling, mTOR signaling, VEGF/VEGFR and c-Met signaling. KRT15, INHBA, MATN3, and AGT are significantly associated with the prognosis of GC patients.
CONCLUSION
Our study identified several DEGs regulated by aberrant DNA methylation in GC. The mechanism of DNA methylation in the carcinogenesis and development of GC could be further explored in these genes, especially KRT15, INHBA, MATN3, and AGT.
目的
本研究旨在鉴定胃癌（GC）中异常甲基化和差异表达的基因（DEGs），并探讨其在 GC 发生发展中的潜在作用。
方法
使用 gdc-client 工具从癌症基因组图谱（TCGA）数据库中下载与 GC 相关的原始 RNA-Seq、临床信息和 Illumina Human Methylation 27 Chip 数据。分别使用 R 中的 edgeR 和 limma 包筛选 DEGs 和异常甲基化基因（AMGs）。DEG 鉴定的截断标准为 P < 0.05 和倍数变化（FC）> 2.0，AMG 鉴定的截断标准为 P < 0.05 和 |t| > 2.0。同时为 DEG 和 AMG 的基因被认为在 GC 中受到异常 DNA 甲基化的调控。使用共同基因进行细胞成分、分子功能、生物过程和生物途径等类别中的进一步功能富集分析。
结果
共鉴定出 465 个基因，包括 336 个高甲基化下调基因（DG-Hyper）和 129 个低甲基化上调基因（UGs-Hypo）。细胞成分分析表明，这些基因主要表达在细胞质和质膜中。分子功能和生物过程分析表明，这些基因主要参与细胞通讯、信号转导、细胞生长/维持以及作为转录因子、受体、细胞粘附分子和跨膜受体蛋白酪氨酸激酶的功能。生物途径分析表明，这些基因参与了一些关键途径，包括上皮间质转化、IL3 介导的信号、mTOR 信号、VEGF/VEGFR 和 c-Met 信号。KRT15、INHBA、MATN3 和 AGT 与 GC 患者的预后显著相关。
结论
本研究鉴定了 GC 中受异常 DNA 甲基化调控的几个 DEGs。可以在这些基因中进一步探讨 DNA 甲基化在 GC 发生发展中的机制，特别是 KRT15、INHBA、MATN3 和 AGT。
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