Role of circulating MYCN in recurrence and/or metastasis of hepatocellular carcinoma as a biomarker and/or regulator

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15833
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: QIN Xian-Yang 国立研究開発法人理化学研究所, 開拓研究本部, 研究員 (60756815)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: MYCN / 肝がん / バイオマーカー / 代謝 / 脂質 / がん幹細胞 / オミクス解析 / エクソソーム

Outline of Final Research Achievements

Previous genome-wide transcriptome screen identified that MYCN expression marked an EpCAM+ cancer stem cell (CSC)-like subpopulation and was a candidate therapeutic target for the prevention of hepatocellular carcinoma (HCC). By the combination of LC-TOFMS-based metabolome analysis and RNA-seq-based transcriptome analysis, I found that the content of unsaturated fatty acids was increased in MYCN high expression CSC-like HCC cells and inhibition of lipid desaturation suppressed MYCN gene expression and cell/sphere proliferation of HCC cells. In addition, I succeeded in quantitatively measuring MYCN protein levels in both human serum and the isolated exosome samples. I found that serum protein levels of MYCN expression were significantly higher in HCC patients than that in healthy controls, and were significantly decreased after surgical resection of tumors. These findings suggested MYCN might server as a therapeutic target and novel biomarker for HCC.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

医療技術の進歩により、がん全体の死亡率が低下しつつある中、肝がんは逆に死亡率が増加しているがんの１つである。日本において、肝がんの年間罹患数が約40,000人であるのに対し、年度死亡数は約30,000人であり、極めて死亡率の高いがんである（Hori et al. Jpn J Clin Oncol 2015）。本研究の成果とした血中MYCNを指標とした肝がんの診断や予後・薬効予測バイオマーカーを活用し、患者さんの予後の改善につながることを願っている。