2022 Fiscal Year Final Research Report

Establishment of a Novel Screening Test for Diagnosing Hepatocellular Carcinoma based on a Sensitive DNA Methylation Assay

Research Project

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Project/Area Number	20K08332
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 53010:Gastroenterology-related
Research Institution	Yamaguchi University
Principal Investigator	Yamasaki Takahiro 山口大学, 大学院医学系研究科, 教授 (00304478)
Co-Investigator(Kenkyū-buntansha)	末廣寛山口大学, 大学院医学系研究科, 准教授 (40290978) 高見太郎山口大学, 大学院医学系研究科, 教授 (60511251) 佐伯一成山口大学, 医学部附属病院, 講師 (60634756)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	肝細胞癌 / リキッドバイオプシー / メチル化 / SEPT9
Outline of Final Research Achievements	In recent years, patients with hepatitis virus related hepatocellular carcinoma (HCC) are decreasing in Japan. The patients with non-viral HCC are often diagnosed at an advanced stage. Against this background, the establishment of a novel HCC surveillance system for early HCC detection is required regardless of the etiology of HCC. To solve this problem, we have developed a novel liquid biopsy test based on a sensitive methylated SEPT9 (m-SEPT9) assay. We achieved a test sensitivity of 63.2% for overall HCC and 42% for early HCC. We enrolled 151 HCC patients in the validation study to evaluate its usefulness. The overall positive rate of HCC was 63.6%, and the positive rates for viral and non-viral HCC were 63.3% and 63.9%, respectively, with no significant difference. The positive rate in early HCC (BCLC-stage 0/A) was 45.1%. Therefore, the results in the validation cohort were similar to those in the training cohort, so we could validate the usefulness of our sensitive m-SEPT9 assay.
Free Research Field	肝臓病学
Academic Significance and Societal Importance of the Research Achievements	肝癌は、他の消化器癌に比べ、難治かつ予後不良である。近年は、非ウイルス性肝癌が増加し、進行肝癌で発見されることも多く、早期発見は予後改善の一番の近道であるが、特に非ウイルス性肝癌に対する肝癌サーベイランスによる早期診断の構築はない。本研究成果は、ウイルス性ならびに非ウイルス性肝癌に関係なく、高感度メチル化解析法によるm-SEPT9測定の有用性が証明できたことから意義のある成果である。社会的意義としては、早期肝癌の5年生存率は約70%に対して、ステージIVの進行肝癌では約20%と著明に低下することから、早期発見により、肝癌の死亡者数減少につながり、健康寿命の延伸を実現できる。