Comprehensive molecular characterization of liver cancer and inheritance of the phenotypic traits during tumor recurrence [tissue]. Comprehensive molecular characterization of liver cancer and inheritance of the phenotypic traits during tumor recurrence [tissue]

Hepatocellular carcinoma (HCC) is a heterogeneous disease with a variety of etiological factors, and ranks as the second leading cause of cancer-related mortality worldwide due to multifocal recurrence. Comprehensive molecular evaluation of HCC by multiplatform analysis defined three major subtypes: (1) mitogenic and stem cell-like tumors with chromosomal instability; (2) CTNNB1-mutated tumors displaying DNA hypermethylation; and (3) metabolic syndrome-associated tumors, which included an immunogenic subgroup characterized by macrophage infiltration and favorable prognosis. Although genomic and epigenomic analysis explicitly discriminated HCC with intrahepatic metastasis (IM) from multicentric HCC (MC), the phenotypic similarity between the primary and recurrent tumors was not linked to the IM/MC diagnosis, but rather the integrated classification. Thus, identification of these HCC subtypes provides insights into patient stratification and opportunities for therapeutic development. Overall design: A total of 183 patients who underwent curative hepatic resection for HCC between 2006 and 2013 at Tokyo Medical and Dental University Hospital participated in integrative analysis of classification. Fifteen adjacent liver tissues obtained from patients with metastasis of colorectal cancer who had not received chemotherapy were used as control.

肝细胞癌（Hepatocellular carcinoma, HCC）是一类存在多种致病因素的异质性疾病，因多灶复发特性成为全球范围内第二大癌症相关死亡病因。通过多组学平台分析对HCC开展全面分子鉴定，现已确立三大主要亚型：（1）伴有染色体不稳定性的促有丝分裂干细胞样肿瘤；（2）表现出DNA高甲基化的CTNNB1突变型肿瘤；（3）代谢综合征相关肿瘤，其中包含以巨噬细胞浸润和良好预后为特征的免疫原性亚组。尽管基因组与表观基因组分析可明确区分伴肝内转移（intrahepatic metastasis, IM）的HCC与多中心性HCC（multicentric HCC, MC），但原发肿瘤与复发肿瘤之间的表型相似性并非与IM/MC分型相关，而是与整合分型有关。因此，对这些HCC亚型的鉴定可为患者分层提供理论支撑，并为治疗策略开发创造契机。研究设计概况：本研究共纳入2006年至2013年间于东京医科齿科大学附属医院接受根治性肝切除术的183例HCC患者，用于开展分型整合分析。另选取15份来自未接受化疗的结直肠癌肝转移患者的癌旁肝组织作为对照。