Identification of metastasis-associated genes based on methylome and chromosome analyses and it's clinical application

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09382
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kindai University
• Principal Investigator: NISHIDA Naoshi 近畿大学, 医学部, 准教授 (60281755)
• Research Collaborator: KUDO Masatoshi ; KAIDO Toshimi ; TANAKA Shinji
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 肝細胞癌 / 転移 / ゲノム / エピゲノム / クロモゾーム / 化学療法

Outline of Final Research Achievements

We clarify molecular features of aggressive HCC, and establish a molecular scoring system that predicts metastasis after curative treatment. In total, 125 HCCs were examined for genome methylome and chromosomal analyses; molecular subclasses and risk score were determined. Next, HCC patients who underwent liver transplantation were analyzed for molecular risk score and metastatic recurrence; survival analyses were validated using a dataset of 376 HCC cases from the Cancer Genome Atlas (TCGA). Molecular risks, that consisted with presence of TP53 mutation, high FAL, global hypomethylation, and absence of CTNNB1 mutation were noted to predict shorter recurrence-free survival in both liver transplantation cohort (p = 0.0090 by log-rank test). and TCGA cohort (p = 0.0076). We concluded that molecular score could predict metastatic recurrence after curative treatments, and could be a marker for considering systemic therapy for HCC patients.

Free Research Field

消化器内科学、肝臓病学、臨床腫瘍学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

近年、肝癌の薬物療法は急速に発展し、肝動脈塞栓術(TACE)の奏効率に近づいている。一方、TACEは肝機能を悪化させるため、TACE後の転移再発のリスクの高い群では薬物療法を先行させるべきとの考えが広がっている。しかし、現在、TACE後の転移再発を予測することは困難である。さらに、肝切除においても、転移再発のリスクの高い群ではアジュバント、ネオアジュバントとしての薬物療法の適応を考慮すべきである。本研究成果は、肝癌転移再発の高リスク群を同定する分子スコアの開発であり、肝癌のマネージメントにおける意義は大きい。