Elucidation of the molecular mechanism and carcinogenic mechanism of gastric adenocarcinoma of fundic-gland type using comprehensive gene expression analysis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15940
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Fukagawa Kazushi 東京大学, 医学部附属病院, 届出研究員 (80882175)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 胃底腺型胃癌 / 網羅的遺伝子発現解析 / NKX2-1/TTF-1

Outline of Final Research Achievements

The comprehensive gene expression analysis of Gastric adenocarcinoma of fundic-gland type (GA-FG) was performed for the first time. GA-FG showed significantly different gene expression profile from well-differentiated adenocarcinoma of conventional gastric cancer. Bioinformatics analysis showed that NKX2-1/TTF-1 and its downstream genes, such as SFTPB, SFTPC, and SCGB3A2, are specifically expressed in cases of GA-FG. Moreover, immunohistochemical analysis confirmed that NKX2-1/TTF-1 and SFTPB are expressed at higher levels in GA-FG tumors than in the normal mucosa. We also demonstrated that NKX2-1/TTF-1 can regulate downstream target genes in both AGS and NUGC4 cells. Interestingly, NKX2-1/TTF-1, a tissue-specific transcription factor that is essential for the development of the lungs and thyroid, is ectopically expressed in GA-FG and can regulate downstream genes in the GA-FG tumor. This suggests that NKX2-1/TTF-1 plays an important role in the developmentof GA-FG.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

肺に特異的に発現する転写因子であるNKX2-1/TTF-1 とその下流遺伝子 (SFTPB、SFTPC、SCGB3A2 など) が胃底腺型胃癌に特異的に発現していることを示し、免疫組織化学染色にてNKX2-1/TTF-1 および SFTPB が発現していることを確認した。さらに胃癌細胞株においてもNKX2-1/TTF-1が下流の標的遺伝子を調節できることも初めて実証した。これらの知見は今後、胃底腺型胃癌の解明に大きく寄与するものと考える。