| International Session（Symposium）1(JSGE・JGES・JSH・JSGS・JSGCS) |
| Thu. October 31st 9:00 - 11:30 Room 11: Portopia Hotel South Wing Topaz |
| Precancerous nature of intestinal metaplasia demonstrated by methylome and single cell ATAC-seq analysis | |||
| Chihiro Takeuchi1,2, Mitsuhiro Fujishiro1, Toshikazu Ushijima2 | |||
| 1Department of Gastroenterology, The University of Tokyo Hospital, 2Department of Epigenomics, Institute for Advanced Life Sciences, Hoshi University | |||
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| Objective. The presence of intestinal metaplasia (IM) is a risk factor for gastric cancer. However, it is still controversial whether IM is precancerous or not. Here, we aimed to explore the precancerous nature of IM by analyzing epigenetic alterations. Design. Genome-wide DNA methylation analysis was conducted by EPIC BeadArray using IM and non-IM crypts. ChIP-seq for H3K27ac, and single-cell ATAC-seq were conducted using IM mucosa. Results. IM crypts had a methylation profile unique from that of non-IM crypts, showing extensive DNA hypermethylation in promoter regions with CpG islands, including those of tumor suppressor genes. The IM-specific methylation profile was carried into gastric cancer more frequently than expected, and was associated with good overall survival. IM organoids had high NOS2 expression, and NOS2 induction led to aberrant DNA methylation by increasing DNMT activity. IM mucosa showed enhancer reprogramming involving NOS2 expression, and IM cells had open chromatin of NOS2. Moreover, IL-17A, a cytokine secreted by extracellular bacterial infection, up-regulated NOS2 expression. Conclusions. IM cells were considered to have a strong precancerous nature with an increased chance of converting into cancer cells in terms of the specific methylation profile and the accelerated DNA methylation induction due to abnormal NOS2 expression. |
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Index Term 1: Intestinal metaplasia Index Term 2: DNA methylation |
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