Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006 Jiangxi Province, China.
Medical College of Nanchang University, Nanchang, 330006 Jiangxi Province, China.
Dis Markers. 2021 Dec 8;2021:4391133. doi: 10.1155/2021/4391133. eCollection 2021.
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 - (-) 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 -associated GC. DNA methylation data of 28 H-positive and 168 H-negative GC samples were compared and analyzed. We also analyzed the gene expression data of 18 H-positive and 145 H-negative GC cases. Finally, the results were verified by and 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 -positive and -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 ( < 0.05). Moreover, infection decreased HUS1, GSTO2, and TMEM190 expression and . Our study identified HUS1, GSTO2, and TMEM190 as novel methylation markers for -associated GC.
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，人们对 DNA 甲基化模式作为 (-) 相关胃癌 (GC) 标志物的潜力关注甚少。在这项研究中，我们对 DNA 甲基化和基因表达进行了综合分析，以鉴定与 (-) 相关 GC 相关的一些潜在关键表观遗传标志物。比较和分析了 28 例 H 阳性和 168 例 H 阴性 GC 样本的 DNA 甲基化数据。我们还分析了 18 例 H 阳性和 145 例 H 阴性 GC 病例的基因表达数据。最后，通过 qPCR 和 Western blot 实验进行了验证。确定了与 2454 个差异甲基化基因相关的 5609 个差异甲基化区域。从 H 阳性和 H 阴性 GC 病例的基因表达数据中鉴定出 228 个差异表达基因。对筛选出的基因进行功能富集分析。随后，通过 Venn 图获得了 28 个受甲基化调控的基因，并鉴定出 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 ( < 0.05)。此外， 感染降低了 HUS1、GSTO2 和 TMEM190 的表达水平，而 miR-199a-5p 过表达则逆转了这种下调。我们的研究确定 HUS1、GSTO2 和 TMEM190 为新型与 (-) 相关 GC 的甲基化标志物。
