HNF4A-Bridging the Gap Between Intestinal Metaplasia and Gastric Cancer

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-04-26 DOI:10.1177/11769343241249017

Yihang Zhao, Hong Tang, Jianhua Xu, Feifei Sun, Yuanyuan Zhao, Yang Li

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引用次数: 0

Abstract

Background:Intestinal metaplasia (IM) of gastric epithelium has traditionally been regarded as an irreversible stage in the process of the Correa cascade. Exploring the potential molecular mechanism of IM is significant for effective gastric cancer prevention.Methods:The GSE78523 dataset, obtained from the Gene Expression Omnibus (GEO) database, was analyzed using RStudio software to identify the differently expressed genes (DEGs) between IM tissues and normal gastric epithelial tissues. Subsequently, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Gene Set Enrichment Analysis (GESA), and protein-protein interaction (PPI) analysis were used to find potential genes. Additionally, the screened genes were analyzed for clinical, immunological, and genetic correlation aspects using single gene clinical correlation analysis (UALCAN), Tumor–Immune System Interactions Database (TISIDB), and validated through western blot experiments.Results:Enrichment analysis showed that the lipid metabolic pathway was significantly associated with IM tissues and the apolipoprotein B ( APOB) gene was identified in the subsequent analysis. Experiment results and correlation analysis showed that the expression of APOB was higher in IM tissues than in normal tissues. This elevated expression of APOB was also found to be associated with the expression levels of hepatocyte nuclear factor 4A ( HNF4A) gene. HNF4A was also found to be associated with immune cell infiltration to gastric cancer and was linked to the prognosis of gastric cancer patients. Moreover, HNF4A was also highly expressed in both IM tissues and gastric cancer cells.Conclusion:Our findings indicate that HNF4A regulates the microenvironment of lipid metabolism in IM tissues by targeting APOB. Higher expression of HNF4A tends to lead to a worse prognosis in gastric cancer patients implying it may serve as a predictive indicator for the progression from IM to gastric cancer.

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HNF4A--弥合肠增生与胃癌之间的鸿沟

背景：胃上皮的肠化生（Intestinal metaplasia，IM）传统上被认为是科雷亚级联过程中的一个不可逆阶段。方法：使用 RStudio 软件分析从基因表达总库（GEO）数据库中获得的 GSE78523 数据集，以确定 IM 组织与正常胃上皮组织之间的差异表达基因（DEGs）。随后，利用基因本体（GO）分析、京都基因组百科全书（KEGG）富集分析、基因组富集分析（GESA）和蛋白-蛋白相互作用（PPI）分析来寻找潜在基因。结果：富集分析表明，脂质代谢通路与IM组织显著相关，并在随后的分析中发现了载脂蛋白B（APOB）基因。实验结果和相关分析表明，IM 组织中 APOB 的表达高于正常组织。研究还发现，APOB 的高表达与肝细胞核因子 4A （HNF4A）基因的表达水平有关。研究还发现，HNF4A 与胃癌的免疫细胞浸润有关，并与胃癌患者的预后有关。结论：我们的研究结果表明，HNF4A 通过靶向 APOB 调节 IM 组织中脂质代谢的微环境。结论：我们的研究结果表明，HNF4A通过靶向APOB调节IM组织中的脂质代谢微环境，HNF4A表达越高，胃癌患者的预后越差。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.