Peritoneal metastasis Prediction by exosome in washing ascites for gastric cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16321
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kumamoto University
• Principal Investigator: Harada Kazuto 熊本大学, 病院, 特任助教 (70608869)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 胃癌 / 腹膜播種 / ゲノム解析 / 次世代シークエンス / Exsosome / 腫瘍免疫 / 腫瘍微小環境

Outline of Final Research Achievements

We identified distinct alterations in peritoneal carcinomatosis versus primary lesion in patients with gastric adenocarcinoma (GAC). Alterations associated with aggressive peritoneal carcinomatosis phenotypes emerged with increased mutations in TP53, CDH1, TAF1 and KMT2C, higher level of ’clock-like’ mutational signature, increase in whole-genome doublings, chromosomal instability (particularly, copy number losses), reprogrammed microenvironment, enriched cell cycle pathways, MYC activation and impaired immune response. Integrated analysis identified two main molecular subtypes: ’mesenchymal-like’ and ’epithelial-like’ with discriminating response to chemotherapy (31% vs 71%).

Free Research Field

腫瘍学

Academic Significance and Societal Importance of the Research Achievements

胃癌の腹膜播種は最も多くみられる転移、再発形式であり、その予後は極めて不良である。腹膜播種の分子生物学的発生メカニズムを解明し、早期診断のバイオマーカーや新規治療戦略を同定することで胃癌の予後を向上させると思われる。我々は胃癌腹膜播種症例の腹水細胞のゲノム解析を行い、腹膜に転移した悪性細胞に特徴的な遺伝子変異を同定した。さらに、免疫抑制に関与するTIM-3の発現が腹水腫瘍細胞の免疫逃避に関与している可能性が明らかにされた、あらたな免疫治療の創薬が期待される