Identification of circulating stromal/cancer cell population detected in hepatocellular carcinoma.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02792
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kanazawa University
• Principal Investigator: Yamashita Taro 金沢大学, 附属病院, 准教授 (90377432)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 肝細胞癌 / 癌幹細胞

Outline of Final Research Achievements

Hepatocellular carcinoma is the second leading cause of cancer death worldwide. In this study, we performed the immunohistochemistry and flow cytometer analysis to identify the cellular heterogeneity of tumor as well as stromal cells. We further performed the single cell transcriptome analysis using peripheral blood mononuclear cells of hepatocellular carcinoma patients. We identified that tumor stromal cells expressing PD1 or CCR6 as well as tumor cells expressing CCL20 were mostly detected at the periphery, not the center of the tumor. We further identified the circulating cell population specifically detected in hepatocellular carcinoma patients. Interestingly, these cell population contained both tumor cells and stromal cells potentially regulating immune system. This study provides important molecular basis of circulating cells potentially be utilized for the diagnosis and treatment of hepatocellular carcinoma.

Free Research Field

消化器病学

Academic Significance and Societal Importance of the Research Achievements

肝癌は世界の悪性腫瘍による死因の第２位を占め、新たな診断治療法の開発が強く求められている。本研究では肝癌組織における間質細胞の多様性に注目、特に肝癌患者の血液中に存在する細胞集団に着目、健常人、慢性肝炎、肝硬変患者では存在せず、肝癌患者においてのみ出現する細胞集団を1細胞トランスクリプトーム解析により同定した。これらの細胞集団は肝癌の悪性度や免疫応答制御に関わる細胞集団である可能性がトランスクリプトームデータから示唆されている。今回の研究成果を応用することで新たな高悪性度肝癌の診断、治療の標的分子としての有用性を検討することが可能となり、大きな学術的、社会的意義を有する。