Guiding the immunotherapy for breast cancer based on the lipid profiling of extracellular vesicles

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08664
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Kyoto University
• Principal Investigator: Kawashima Masahiro 京都大学, 医学研究科, 助教 (80766676)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 乳癌 / 細胞外小胞 / 脂質代謝 / リキッドバイオプシー

Outline of Final Research Achievements

In this study, we investigated whether breast cancer, its subtypes and clinical stages, can be diagnosed from differences in the lipid profile of circulating extracellular vesicles (EVs) using plasma samples from a cohort of Japanese breast cancer patients and healthy subjects. We found that sucrose cushion ultracentrifugation was the best method to isolate high-quality EVs from plasma samples without contamination of lipoproteins. We analyzed samples from two independent cohorts consisting of breast cancer patients, patients with benign breast disease and healthy subjects, and successfully developed a breast cancer diagnostic model based on differences in the lipid composition of EVs. Exploratory analyses also suggested that the lipid profile of EVs may be used for the prediction of clinical stage and subtype of breast cancer.

Free Research Field

乳腺外科学

Academic Significance and Societal Importance of the Research Achievements

血漿由来EVの脂質のプロファイリングを、乳がんの有無、病期やサブタイプを診断できるリキッドバイオプシーとして応用できる可能性が示唆された。EVの脂質組成が乳がん診断に応用できるとした報告はこれまでに前例が無く、ユニークな研究結果であると考えられる。血液による診断は、従来の病理組織診断に比べるとはるかに低侵襲であり、本成果が患者負担の少ない優れた診断法開発の一助となる可能性がある。ただし、臨床使用に十分な性能を達成するためには、EV分離技術の向上も含めたさらなる技術革新と、より大規模なコホートでの検証が必要である。