Trial to treat gastric cancer via regulating the status of gastrointestinal differentiation

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08612
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: Yamamichi Nobutake 東京大学, 医学部附属病院, 准教授 (30463897)
• Research Collaborator: Tomida Shuta ; Inada Ken-ichi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 胃癌 / 消化管分化

Outline of Final Research Achievements

We found that intestinal differentiation induced by CDX caused growth arrest of several gastric cancer cells. Using the CDX-related gene probe markers, we analyzed gene expression data of many gastric cancer cases and found that gene expression of CDX-positive gastric cancer was clearly closer to that of non-cancerous gastric mucosa than CDX-negative gastric cancer. Based on these results, we concluded that CDX-induced intestinal differentiation can show a tumor suppressive effect on gastric cancer (Cancer Sci 2018, 109: 3853). In addition, in the process of this experiment, we succeeded in developing a method to perform comprehensive gene expression analysis from a small biopsy specimen (about 10ug) of a gastrointestinal tract tumor (J Gastroenterol 2018, 54: 131).

Free Research Field

腫瘍学、病態医化学、分子生物学、消化器病学

Academic Significance and Societal Importance of the Research Achievements

切除が唯一の根治療法とされている胃癌が、分化誘導によって制御できることを発見し、薬物療法に繋がりうる新たな可能性を報告した。また、これまで様々な分類がなされてきた胃癌分類において、予後・悪性度の予測や治療方針の決定の有用性が期待される「消化管分化の視点に基く新しい分類（CDX発現に基づく胃癌分類）」について、詳細な遺伝子発現データの解析に基いた提唱を行った。さらに、消化管腫瘍の微少な生検検体から正確に網羅的な遺伝子発現解析を施行する手法の開発に成功し、将来のオーダーメイド医療（網羅的な遺伝子発現解析に基づく病態予測・治療プラン決定）の基盤となる医療技術を確立した。