Department of Internal Medicine, Health Promotion Center, Seoul National University Hospital, Seoul, Korea.
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Gut Liver. 2023 Sep 15;17(5):741-752. doi: 10.5009/gnl220301. Epub 2023 Jan 31.
BACKGROUND/AIMS: Altered DNA methylation is a key mechanism of epigenetic modification in gastric cancer (GC). This study aimed to evaluate the changes in epigenetic and genetic expression of multiple Rho GTPases in -related gastric carcinogenesis by comparing -positive GCs and negative controls.
The messenger RNA expression and methylation of Rho GTPases (RhoA, Rac1, DOCK180, ELMO1, and CDC42) were evaluated in -negative (control) human gastric tissues and -positive GCs by using real-time reverse transcription-polymerase chain reaction and the quantitative MethyLight assay, respectively. Changes in expression and methylation levels of the genes were also compared between -eradicated and -persistent GCs at 1-year follow-up.
In GCs, the methylation and expression levels of DOCK180 and ELMO1 were higher than in controls, while RhoA and Rac1 had lower levels than controls. CDC42 had the same expression pattern as DOCK180 and ELMO1 without DNA methylation. Although methylation levels of DOCK180 and ELMO1 had no difference between -eradicated and -persistent GCs at the index endoscopic resection, those of -persistent GCs increased and -eradicated GCs decreased for 1 year. The expression levels of DOCK180, ELMO1, and CDC42 in -persistent GCs were higher than those in -eradicated GCs over 1 year, unlike those of RhoA and Rac1. The methylation levels at index and the degrees of change over time of RhoA and Rac1 had no difference between -persistent and -eradicated GCs.
Epigenetic alterations of DOCK180 and ELMO1 are involved in -related gastric carcinogenesis. This epigenetic field could be improved by eradication.
背景/目的：DNA 甲基化改变是胃癌（GC）中表观遗传修饰的关键机制。本研究旨在通过比较阳性 GC 和阴性对照，评估多个 Rho GTPases 的表观遗传和遗传表达在 -相关胃致癌中的变化。
采用实时逆转录-聚合酶链反应和定量甲基化 Light 检测法，分别评估 Rho GTPases（RhoA、Rac1、DOCK180、ELMO1 和 CDC42）在阴性（对照）人胃组织和阳性 GC 中的信使 RNA 表达和甲基化。还比较了在 1 年随访中根除和持续性 GC 之间基因表达和甲基化水平的变化。
在 GC 中，DOCK180 和 ELMO1 的甲基化和表达水平高于对照组，而 RhoA 和 Rac1 的水平低于对照组。CDC42 的表达模式与 DOCK180 和 ELMO1 相同，没有 DNA 甲基化。尽管在指数内镜切除时，DOCK180 和 ELMO1 的甲基化水平在根除和持续性 GC 之间没有差异，但在 1 年内，持续性 GC 的甲基化水平增加，而根除性 GC 的甲基化水平降低。在 1 年内，持续性 GC 中 DOCK180、ELMO1 和 CDC42 的表达水平高于根除性 GC，而 RhoA 和 Rac1 则不同。在持续性和根除性 GC 之间，RhoA 和 Rac1 的指数甲基化水平及其随时间变化的程度没有差异。
DOCK180 和 ELMO1 的表观遗传学改变参与了 -相关的胃致癌作用。这种表观遗传学领域可以通过根除来改善。
