2021 Fiscal Year Final Research Report

The study of emergence of cancerous gland in chronic gastritis through three dimensional histological structure and genetic analysis

Research Project

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Project/Area Number	19K08389
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	Niigata University
Principal Investigator	Yagi Kazuyoshi 新潟大学, 医歯学総合病院, 特任教授 (20220121)
Co-Investigator(Kenkyū-buntansha)	寺井崇二新潟大学, 医歯学系, 教授 (00332809) 橋本哲新潟大学, 医歯学総合研究科, 客員研究員 (10768667) 土屋淳紀新潟大学, 医歯学総合病院, 講師 (70464005)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	胃癌 / 慢性胃炎 / H.pylori / 腸上皮化生 / MUC6 / CDX2 / 幽門腺化生
Outline of Final Research Achievements	According to our investigation, the following was realized: in chronic gastritis, chief cell changed to MUC6 cell which formed pyloric gland metaplasia and furthermore changed to intestinal metaplasia in expressing of CDX2.On the other hand, cancerous cells occurred from MUC6 cells, especially in CDX2-positive cell. We supposed that cancerous cells developed from MUC6 cells by trigger of expression of CDX2.We analyzed genes of cancerous tissue, pyloric gland metaplasia and intestinal metaplasia in three cases of gastric cancer. In two of three cases, the pyloric gland metaplasia and cancer had a close relationship, whereas the intestinal metaplasia and cancer were distantly related. We thought that in these two cancers, the pyloric gland metaplasia and cancer were closely related genetically, and the intestinal metaplasia and cancer were distantly related, suggesting that these cancers did not follow the metaplasia-dysplasia-cancer sequence.
Free Research Field	消化器内科
Academic Significance and Societal Importance of the Research Achievements	H.pylori感染が慢性胃炎と胃癌発生にも強く関与していることは広く認知されている。しかしその機序が理解されていない。我々は主細胞がMUC6腺管に先祖返りし、さらにCDX2発現が癌化に関与しているという新しい理論を構築した。腸上皮化生が出現した胃から発癌することより腸上皮化生からの発癌が今も広く受け入れられている。しかし腸上皮化生からの癌の発生の考えでは実際の症例で矛盾することも多い。MUC6から癌が発生しCDX2発現がそれに関わっているという理論により、腸上皮化生が出現した胃はすでにCDX2は発現しており、癌発生リスクは高いことも説明できる。胃癌発生リスクを科学的に証明できた。