Novel suppression of gastric carcinogenesis based on the spatiotemporal elucidation of H. pylori genome alterations identified using clinical samples

• Project/Area Number: 19H03521
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Yamamoto Hiroyuki 聖マリアンナ医科大学, 医学研究科, 教授 (40332910)
• Co-Investigator(Kenkyū-buntansha): 伊東 文生 聖マリアンナ医科大学, 医学部, 教授 (90223180) ; 松尾 康正 聖マリアンナ医科大学, 医学部, 講師 (70724756)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
• Keywords: H. pylori / ゲノム解析 / ゲノム多様性 / 胃洗浄廃液 / 胃癌

Outline of Research at the Start

世界の全人口の半数以上がピロリ菌に感染しているが、胃癌を発症するのは一部であり、これをピロリ菌ゲノムの多様性で説明できるか、ゲノム解析により明らかにする。内視鏡検査時にピロリ菌感染・薬剤感受性・発癌リスクを可視化できるバイオチップを開発し、臨床応用を目指す。これにより、健診への導入や病原体ゲノムの時空間的解析による、感染症に基づくさまざまな癌の分子機構解明へ寄与する。

Outline of Final Research Achievements

Helicobacter pylori is a primary factor in the pathogenesis of gastric cancer. A clear understanding of the H. pylori genome factors underlying gastric cancer remains elusive. Based on long read next-generation sequencing of gastric wash and other samples, we identified gastric cancer-specific important alterations in the H. pylori genome. We revealed that these alterations can be used as novel molecular markers for gastric cancer. We also successfully characterized the functional significance of these alterations in gastric carcinogeneis. These results may help introduce early diagnostic and/or preventive measures for gastric cancer in patients infected with high-risk H. pylori strains. Thus, our findings can be applied to novel suppression of gastric carcinogenesis based on the spatiotemporal elucidation of H. pylori genome alterations identified using clinical samples.

Academic Significance and Societal Importance of the Research Achievements

ピロリ菌およびヒトゲノムの解析に基づく胃癌の本質的な基礎医学的分子病態の解明という点で、学術的意義が大きい。また、診断から除菌治療までの迅速遺伝子判定システムなどの臨床応用開発につながる成果であることから、社会的意義も大きい。