Multi-omix analyses of gastric intramucosal neoplasia based on histological subtypes.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07412
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Iwate Medical University
• Principal Investigator: Sugai Tamotsu 岩手医科大学, 医学部, 教授 (20187628)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 胃粘膜内腫瘍 / 組織型 / オミックス解析 / 腺窩上皮型癌 / 手繋ぎ型癌 / 組織グレード / 腫瘍発生学 / 分子異常

Outline of Final Research Achievements

We attempted to identify the molecular profiles of gastric intramucosal neoplasia (IMN; low-grade dysplasia, LGD; high-grade dysplasia, HGD; intramucosal cancer, IMC) by assessing somatic copy number alterations (SCNAs) stratified by microsatellite status (microsatellite stable, MSS; microsatellite instable, MSI). In addition, we aimed to identify the clinicopathological characteristics and molecular alterations contributing to the development of gastric foveolar neoplasia/dysplasia, and crawling type gastric adenocarcinoma. The SCNA pattern of LGD was different from that of HGD and IMC. Moreover, IMNs with the MSI phenotype could be categorized into two subtypes: high frequency of SCNAs and low frequency of SCNAs. Second, foveolar and crawling types were characterized by SCNAs at multiple foci relative to conventional type gastric adenocarcinoma. Molecular profiles may be useful for elucidation of the mechanisms of early gastric carcinogenesis.

Free Research Field

病理学、消化器腫瘍学、消化器病理学、病理診断学

Academic Significance and Societal Importance of the Research Achievements

これまで分化型粘膜内腫瘍の組織像との対応関係をゲノムワイドな網羅的解析によって明らかにした報告は皆無に近い。本研究は類型化された粘膜内腫瘍の組織像とマルチオミックス解析による分子解析との関連性を明らかにした。粘膜内腫瘍の組織像と分子異常との相関性、を明らかにすることは胃癌発生の初期の形態像に基づいた分子腫瘍発生の機序を解明し、胃癌の多様な組織発生の個別的な理解を深化させることに貢献できた。現在の胃粘膜内癌の治療は内視鏡的に行われているが、組織型に基づいたより個別的な治療の可能性について貢献できる研究であった。