Discovery and Validation of Novel Methylation Markers in Helicobacter pylori-Associated Gastric Cancer.
Discovery and Validation of Novel Methylation Markers in Helicobacter pylori-Associated Gastric Cancer.
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DOI：
10.1155/2021/4391133
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Hu Y
中科院分区：
文献类型：
--
作者：
Wang H;Li NS;He C;Xie C;Zhu Y;Lu NH;Hu Y
先前的研究表明，异常甲基化是大多数人类癌症发病机制中的早期关键事件，有助于肿瘤的发展。然而，DNA 甲基化模式作为幽门螺杆菌 (H. pylori) 相关胃癌 (GC) 标记的潜力却很少受到关注。在这项研究中，对 DNA 甲基化和基因表达进行了综合分析，以确定幽门螺杆菌相关 GC 中一些潜在的关键表观遗传标记。对28份H. pylori阳性和168份H. pylori阴性GC样本的DNA甲基化数据进行了比较和分析。我们还分析了18例幽门螺杆菌阳性和145例幽门螺杆菌阴性GC病例的基因表达数据。最后通过体外和体内实验验证了结果。共鉴定出与 2454 个差异甲基化基因相关的 5609 个差异甲基化区域。从幽门螺杆菌阳性和幽门螺杆菌阴性GC病例的基因表达数据中，共鉴定出228个差异表达基因。对筛选的基因进行功能富集分析。随后，我们通过维恩图获得了28个受甲基化调节的基因，并确定了5个受高甲基化下调的基因（GSTO2、HUS1、INTS1、TMEM184A和TMEM190）。 HUS1、GSTO2 和 TMEM190 在 GC 中的表达水平低于相邻样本 (P < 0.05)。此外，幽门螺杆菌感染降低了体外和体内 HUS1、GSTO2 和 TMEM190 的表达。我们的研究确定 HUS1、GSTO2 和 TMEM190 是幽门螺杆菌相关 GC 的新型甲基化标记物。
Previous studies have shown that abnormal methylation is an early key event in the pathogenesis of most human cancers, contributing to the development of tumors. However, little attention has been given to the potential of DNA methylation patterns as markers for Helicobacter pylori- (H. pylori-) associated gastric cancer (GC). In this study, an integrated analysis of DNA methylation and gene expression was conducted to identify some potential key epigenetic markers in H. pylori-associated GC. DNA methylation data of 28 H. pylori-positive and 168 H. pylori-negative GC samples were compared and analyzed. We also analyzed the gene expression data of 18 H. pylori-positive and 145 H. pylori-negative GC cases. Finally, the results were verified by in vitro and in vivo experiments. A total of 5609 differentially methylated regions associated with 2454 differentially methylated genes were identified. A total of 228 differentially expressed genes were identified from the gene expression data of H. pylori-positive and H. pylori-negative GC cases. The screened genes were analyzed for functional enrichment. Subsequently, we obtained 28 genes regulated by methylation through a Venn diagram, and we identified five genes (GSTO2, HUS1, INTS1, TMEM184A, and TMEM190) downregulated by hypermethylation. HUS1, GSTO2, and TMEM190 were expressed at lower levels in GC than in adjacent samples (P < 0.05). Moreover, H. pylori infection decreased HUS1, GSTO2, and TMEM190 expression in vitro and in vivo. Our study identified HUS1, GSTO2, and TMEM190 as novel methylation markers for H. pylori-associated GC.
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影响因子：
4.3
作者：
Lazăr DC;Avram MF;Romoșan I;Cornianu M;Tăban S;Goldiș A
通讯作者：
Goldiș A
影响因子：
3.8
作者：
Nishimura, Hitoshi;Gupta, Surabhi;Primakoff, Paul
通讯作者：
Primakoff, Paul
影响因子：
4.5
作者：
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通讯作者：
Mancini GMS
影响因子：
158.5
作者：
Choi, Ii Ju;Kim, Chan Gyoo;Joo, Jungnam
通讯作者：
Joo, Jungnam
影响因子：
4.5
作者：
Lyndaker AM;Lim PX;Mleczko JM;Diggins CE;Holloway JK;Holmes RJ;Kan R;Schlafer DH;Freire R;Cohen PE;Weiss RS
通讯作者：
Weiss RS