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. 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.