DNA methylation and IDH mutations in intrahepatic cholangiocarcinoma

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16418
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kumamoto University
• Principal Investigator: Miyata tatsunori 熊本大学, 生命科学研究部(医), 特定研究員 (80594887)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 肝内胆管癌 / LINE-1 / DNAメチル化 / エピジェネティクス / IDH変異

Outline of Final Research Achievements

Methylation of LINE-1 promoter region in cancerous and noncancerous areas was measured in resected samples of intrahepatic cholangiocarcinoma (ICC). In the analysis of clinicopathologic factors and LINE-1 methylation levels, the hypomethylated group had a significantly higher frequency of lymph node metastases (p=0.04) and a significantly worse prognosis in overall survival (Log-rank p=0.045), but there was no difference between the two groups in recurrence-free survival.
IDH mutations (IDH1 and IDH2) were found in 9 of 72 patients (12.5%), including 8 patients (11.1%) with IDH1 mutation and 1 patient (1.4%) with IDH2 mutation. The relationship between clinicopathological factors and IDH mutations was evaluated in the 67 patients for whom patient information was available, and no statistically significant differences in clinicopathological factors, prognosis, or LINE-1 methylation levels were found between the two groups.

Free Research Field

消化器外科、肝胆膵癌

Academic Significance and Societal Importance of the Research Achievements

ICCは予後不良な肝がんの一組織型である。術後も早期に再発することから、その予後を予測し再発や予後が不良なICCを同定することは重要である。本研究により、ICCのLINE-1メチル化が低い症例はリンパ節転移が有意に多く、肝切除後の予後が悪かった。しかしながら、IDH変異との関連は示されなかった。より大きなサンプルを用いてLINE-1メチル化を用いたICCの予後予測についてさらなる検討が必要である。