Huang Hongyun, Xie Lang, Feng Xiaoxuan, Zheng Zheng, Ouyang Juntao, Li Yan, Yu Jinlong
Department of General Surgery of Zhujiang Hospital, Southern Medical University, Guangzhou, China.
The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.
Ann Transl Med. 2021 Sep;9(18):1414. doi: 10.21037/atm-21-3211.
Gastric adenocarcinoma (GAC), a common type of gastric cancer, poses a significant public health threat worldwide. This study aimed to determine the transcriptional regulatory mechanisms of GAC.
HTSeq-FPKM raw data were obtained from The Cancer Genome Atlas Stomach Adenocarcinoma data collection. Subsequently, the limma package in R was used to identify differentially expressed genes (DEGs). Differentially methylated genes (DMGs), DEGs, and differentially expressed microRNAs (miRNAs) in normal, and tumor tissues of the same patients were screened and compared using R software tools. A functional enrichment analysis was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) for various DEGs, DMGs, promoter methylation, and miRNAs. DEG-specific methylation and transcription factors were analyzed using ENCODE ChIP-seq.
DEGs were centrally modified by the histone trimethylation of lysine 27 on histone H3 (H3K27me3). Upstream transcription factors of DEGs were enriched in different ChIP-seq clusters, such as Forkhead Box M1, E2F Transcription Factor 4, and suppressor of zest 12. Integrated regulatory networks of DEGs, promoter methylation, and miRNAs were constructed. Two miRNAs (hsa-mir-1 and hsa-mir-133a) and four DEGs (A disintegrin and metalloproteinase domain 12, transcription factor AP-2 alpha, solute carrier family 5 member 7, and cadherin 19) separately played important roles in the integrated regulatory network. Therefore, these DEGs, DMGs, promoter methylation, and miRNAs may play an important role in GAC pathogenesis.
In summary, the present study results provide insights into the oncogenesis and progression of GAC, thus accelerating the development of novel targeted GAC therapies.
胃腺癌（GAC）是胃癌的常见类型，在全球范围内对公众健康构成重大威胁。本研究旨在确定GAC的转录调控机制。
从癌症基因组图谱胃腺癌数据集中获取HTSeq-FPKM原始数据。随后，使用R语言中的limma软件包来识别差异表达基因（DEG）。使用R软件工具筛选并比较同一患者正常组织和肿瘤组织中的差异甲基化基因（DMG）、DEG和差异表达的微小RNA（miRNA）。使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）对各种DEG、DMG、启动子甲基化和miRNA进行功能富集分析。使用ENCODE染色质免疫沉淀测序（ChIP-seq）分析DEG特异性甲基化和转录因子。
DEG由组蛋白H3上赖氨酸27的组蛋白三甲基化（H3K27me3）进行中心修饰。DEG的上游转录因子富集于不同的ChIP-seq簇中，如叉头框M1、E2F转录因子4和zest 12抑制因子。构建了DEG、启动子甲基化和miRNA的综合调控网络。两种miRNA（hsa-mir-1和hsa-mir-133a）和四个DEG（解整合素和金属蛋白酶结构域12、转录因子AP-2α、溶质载体家族5成员7和钙黏蛋白19）分别在综合调控网络中发挥重要作用。因此，这些DEG、DMG、启动子甲基化和miRNA可能在GAC发病机制中发挥重要作用。
总之，本研究结果为GAC的肿瘤发生和进展提供了见解，从而加速了新型GAC靶向治疗的开发。
