Development of an early diagnostic marker for hepatocellular carcinoma associated with lifestyle-related diseases: analysis of circulating extracellular vesicles

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K11640
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Yamaguchi University
• Principal Investigator: Yamaguchi Natsu 山口大学, 大学院医学系研究科, 助教 (40450671)
• Co-Investigator(Kenkyū-buntansha): 佐伯 一成 山口大学, 医学部附属病院, 講師 (60634756) ; 田邉 剛 山口大学, 大学院医学系研究科, 教授 (80260678) ; 中上 裕有樹 下関市立大学, 経済学研究科, 准教授 (30843304)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: hepatocellular carcinoma / extracellular vesicles

Outline of Final Research Achievements

In this study, from the perspective of developing a minimally invasive and highly accurate diagnostic marker for early detection of non-B non-C hepatocellular carcinoma in patients with lifestyle-related diseases, which are risk factors, we aimed to identify proteins that are highly expressed in extracellular vesicles secreted by liver cancer cells. We purified extracellular vesicles from the culture supernatants of the hepatocellular carcinoma cell line HuH-7 and the normal liver cell line Fa2N-4, and performed proteomic analysis. As a result, we identified 109 proteins that were expressed only in extracellular vesicles derived from HuH-7 cells. Among these, we selected 11 proteins with high abundance as marker candidates, which had not been reported to be expressed in human blood samples other than liver cancer.

Free Research Field

予防医学

Academic Significance and Societal Importance of the Research Achievements

近年急増する非Ｂ非Ｃ型肝癌は、糖尿病など生活習慣病をリスク要因とするが、ハイリスク群の同定方法が確立していない。早期発見には、合併率７割である生活習慣病との高い識別能をもつ低侵襲な診断法が必要である。本研究では、高い肝癌識別力をもつ診断マーカー候補としてEV発現タンパク質に着目し、培養細胞を用いた解析によりマーカー候補となるタンパク質を同定した。今後、マーカー候補の臨床的有用性を検証し研究を発展させることにより、血液検体を用いた肝癌の早期診断法の開発や、ex vivoでの腫瘍評価につながることが期待される。