| Project/Area Number |
15K08955
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Nagoya City University |
|---|
Principal Investigator |
Hayashi Kazuki 名古屋市立大学, 大学院医学研究科, 講師 (00405200)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
溝下 勤 名古屋市立大学, 大学院医学研究科, 講師 (40347414)
岡本 泰幸 名古屋市立大学, 大学院医学研究科, 助教 (60444973)
|
|---|
| Project Period (FY) |
2015-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | 胃がん / エピジェネティクス / 胃癌 |
|---|
| Outline of Final Research Achievements |
We analyzed mRNA profile and DNA methylation status, gene mutations of Gastric cancer. We divided into 4 groups from mucin phenotype based on expression status of MUC2、CDX2、VIL1、ALPI. In Null type gastric cancer, which do not express any phenotypic markers, aberrant DNA methylation were enriched, suggesting that these are CpG island methylator phenotype (CIMP). Mutation rate of Null Type gastric cancer is higher than that of the other type gastric cancer because of silencing of mismatch repair gene induced by DNA methylation. PIK3CA mutation were enriched in Null type gastric cancer. It means EB virus associated gastric cancer were involved in Null type gastric cancer. Expression of CD274 and PDCD1, which known as target of immune chechpoint inhibitor, were higher than that of the other group. These data suggest that immune chechpoint inhibitor might be effective in Null type gastric cancer.
|
| Academic Significance and Societal Importance of the Research Achievements |
胃癌の粘液性質の分類で、形質発現を認めないNull型関して、その分子生物学的な特徴は十分に報告されていない。また、Null型は予後が悪いことでも知られており、適切な薬物療法の開発が望まれている。本研究でNull型胃癌はDNAメチル化を多く有し、悪性化にDNAメチル化が関連していることがわかった。また、EBウイルス胃癌もNull型に多く含まれることや、CD274とPDCD1の発現が高値であることからも免疫チェックポイント阻害剤が有効である可能性が示唆された。
|
