Identification of biomarker in intrahepatic recurrence of hepatocellular carcinoma through extracellular vesicles

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09146
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Osaka University
• Principal Investigator: Noda Takehiro 大阪大学, 医学系研究科, 助教 (50528594)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 肝細胞癌 / microRNA / 予後 / 手術 / リキッドバイオプシー / 前転移ニッチ

Outline of Final Research Achievements

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death. Recently, exosomal microRNAs(miRNAs) have been reported to have a role in the formation of the pre-metastatic niche and as promising biomarkers in patients with malignancy. Here we aimed to clarify the molecular mechanisms of intrahepatic metastasis and to identify a novel biomarker miRNA in patients with HCC. The miRNAs (miR-638, miR-663a, miR-3648, and miR-4258) could attenuate
endothelial junction integrity by inhibiting VE-cadherin and ZO-1 expression. In patients with HCC, higher serum exosomal miR-638 expression was associated with
tumor recurrence. In conclusion, the miRNAs secreted from a highly metastatic cancercell can promote vascular permeability via downregulation of endothelial expressionof VE-cadherin and ZO-1. Serum exosomal miR-638 expression holds potential for serving as a significant and independent prognostic marker in HCC.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

リキッドバイオプシーのリソースとしてエクソソームが着目され、様々な研究が行われている。エクソソームの膜タンパクやmiRNAに着目したバイオマーカーの報告があり、いずれにおいても早期診断や術後フォローに応用できる可能性が報告されている。本研究で同定したmiR-638については、肝細胞癌術前の高発現が再発予測マーカーとして応用できる可能性が考えられた。