Investigation of molecular pathology based on quantitative evaluation of intratumor heterogeneity in hepatocellular carcinoma

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07722
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kindai University
• Principal Investigator: Sakai Kazuko 近畿大学, 医学部, 講師 (20580559)
• Co-Investigator(Kenkyū-buntansha): 西尾 和人 近畿大学, 医学部, 教授 (10208134) ; 海堀 昌樹 関西医科大学, 医学部, 教授 (30333199)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 肝細胞癌 / 腫瘍内不均一性 / 遺伝子異常

Outline of Final Research Achievements

Tumor heterogeneity based on copy number variations is associated with the evolution of cancer and its clinical grade. Clonal composition (CC) represents the number of clones based on the distribution of B-allele frequency (BAF) obtained from a genome-wide single nucleotide polymorphism (SNP) array. A higher CC number represents a high degree of heterogeneity. Somatic mutations, total transcriptome, and copy number variation were analyzed in patients with resectable HCC. The samples were classified the heterogeneous tumors as poly-CC (n=26) and the homogeneous tumors as mono-CC (n=8). The patients with poly-CC had a higher rate of early recurrence and a significantly shorter recurrence-free survival period than the mono-CC patients. A transcriptome analysis showed that cell cycle-related pathways were enriched in the poly-CC tumors compared with the mono-CC tumors. Poly-CC HCC is highly proliferative and has a high risk of early recurrence.

Free Research Field

医学

Academic Significance and Societal Importance of the Research Achievements

肝細胞癌における腫瘍の不均一性を数値化し、腫瘍内不均一性の高いpoly-CC腫瘍が術後再発と関連することを明らかにした。コピー数変動及びB-アレル頻度に基づいたClonal composition数による腫瘍内不均一性の指標は、細胞周期関連経路の活性化を伴う増殖性の特徴と関連し、肝細胞癌の分子病態の新たな知見が見いだされた。