Subclassification of gastrointestinal stromal tumor and elucidation of prognostic factors - approach by non-coding RNA

Research Project

Project/Area Number	15K08390
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Human pathology
Research Institution	Japanese Foundation for Cancer Research
Principal Investigator	Takazawa Yutaka 公益財団法人がん研究会, がん研究所病理部, 部長 (50313151)
Research Collaborator	NAGANO Yuko
Project Period (FY)	2015-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000) Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000) Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords	胃消化管間質腫瘍 / 非コードＲＮＡ / microRNA / GIST / 非コードRNA / 悪性度評価 / 消化管間質腫瘍 / 分化 / 悪性度
Outline of Final Research Achievements	This study was aimed to reveal the tumorigenesis and biological behavior of gastrointestinal stromal tumor (GIST) in terms of non-coding RNA expression. Differences of expression among organs and between low grade and high grade were examined. We reviewed c-kit, PDGFRα and other gene mutations and comprehensively analyzed microRNA expression. The expression of microRNAs was not significantly different among different organs (esophagus, stomach, duodenum, jejunum, ileum, colon, rectum, and extragastrointestinal organs), although cluster analysis revealed three groups according to the different organs. Comparison of low grade and high grade groups identified differentially expressed microRNAs, which were associated with cell proliferation and metastatic potential.
Academic Significance and Societal Importance of the Research Achievements	稀少がんの一つであるが消化管に発生する非上皮系の悪性腫瘍で最も頻度の高い胃消化管間質腫瘍（GIST）について、非コードRNA発現の観点から、その腫瘍発生および悪性度評価を解明することを目的とする研究である。GISTの発生頻度や悪性度は発生臓器（食道、胃、小腸、結腸、直腸）により異なることは未解決の問題であったが本研究によって、非コードRNA発現パターンから発生臓器は３つのグループに分かれる傾向があること、GISTの悪性度は細胞増殖や転移能に関係するmicroRNAの発現と関係していること、が見いだされた。これらの結果は臨床におけるGISTの治療戦略に影響を与える可能性がある。