Molecular characterization and therapeutic target identification of gastric cancer with primitive phenotype

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06882
• 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: The University of Tokyo
• Principal Investigator: Ushiku Tetsuo 東京大学, 大学院医学系研究科(医学部), 教授 (60376415)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 胃癌 / 胎児形質 / 免疫回避 / 治療標的

Outline of Final Research Achievements

Based on RNA-seq analysis, we selected gastric carcinomas with a primitive phenotype, which showed increased expression of genes that characterize primitive cells. We found that one of the receptor-type tyrosine kinases is characteristically up-regulated in gastric carcinomas with primitive phenotype. Inhibitor experiments using gastric cancer cell lines showed significant concentration-dependent growth inhibition in cell lines derived from gastric carcinoma with primitive phenotype, and this molecule are considered as promising therapeutic targets. Furthermore, in addition to the frequent acquisition of immune evasion mechanisms such as PD-L1 expression and loss of HLA class I molecules, we discovered that gastric cancer with primitive phenotype specifically expressed high levels of immune evasion molecules associated with acquisition through primitive phenotype transformation as a unique immune evasion mechanism.

Free Research Field

病理学

Academic Significance and Societal Importance of the Research Achievements

胃癌の予防や早期発見が進んでいるが、進行胃がんの予後はいまだ不良であり、胃癌撲滅のためには特に悪性度の高い胃癌の成り立ちを明らかにし、最適な治療方法を確立する必要がある。本研究では、悪性度の高い胃癌の代表である胎児形質胃癌に特徴的な細胞増殖に関連する分子、および腫瘍免疫回避機構の一端を明らかにした。今後はこれらを標的とした治療戦略を確立することで、胎児形質胃癌の個別化医療が推進されると期待される。