2023 Fiscal Year Final Research Report

Gastric cancer and duodenal ulcer - two different mechanisms of gastric disease onset based on Helicobacter pylori infection

Research Project

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Project/Area Number	21K07898
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 53010:Gastroenterology-related
Research Institution	Oita University
Principal Investigator	Akada Junko 大分大学, 医学部, 助教 (30346548)
Co-Investigator(Kenkyū-buntansha)	山岡吉生大分大学, 医学部, 教授 (00544248) 松本昂大分大学, 医学部, 助教 (50609667) 塚本善之大分大学, 医学部, 助教 (00433053) 村上和成大分大学, 医学部, 教授 (00239485)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	ヘリコバクター・ピロリ / 胃癌 / 十二指腸潰瘍 / GWAS解析 / 遊走能 / 胃オルガノイド / IgA
Outline of Final Research Achievements	Helicobacter pylori strains derived from gastric cancer (GC) and duodenal ulcer (DU), were compared using genome-wide gene association analysis, and 11 genes with single nucleotide polymorphisms (SNPs) were identified. Based on the previous report, this study focused on one of them, the dsbG gene and conducted an experimental evaluation. Since DsbG is involved in the motility of bacteria, we created a gene-knockout strain of standard strain 26695, GC-type-SNP or DU-type-SNP complemented strains, and evaluated the motility of each strain. The dsbG-knockout strain lacks motility, however, the gene-complemented strain recovers it. Moreover, the GC-type-SNP introduced strain is equivalent to the DU-type- SNP introduced strain under neutral conditions, but shows higher motility under acidic conditions. We proceeded with the establishment of a gastric organoid infection experimental system. We are also processing with the anti-H. pylori IgA analysis using GC- and DU-patient serum samples.
Free Research Field	分子疫学
Academic Significance and Societal Importance of the Research Achievements	胃癌の主要な誘導因子はピロリ菌であるが、ピロリ菌感染により誘導される胃疾患は、胃炎、胃潰瘍、十二指腸潰瘍、マルトリンパ腫、腸上皮化生、胃癌と多様である。内視鏡的観察や病理組織診断により、萎縮性胃炎から腸上皮化生を経て胃癌に至ると推定されており、また十二指腸潰瘍患者が後に胃癌が発生することはまれであることも指摘されてきた。我々はこの対照的な二つの胃疾患に関連するピロリ菌因子をゲノム解析から見出してきた。本研究では、胃癌発症に関与するこれら細菌因子を実験的に評価し、作用機序に関与する宿主因子や環境因子を見出し、そこから新しい胃癌予防や治療戦略につなげる道を開いてゆく。