Characterization of Cholangiocarcinoma-like Hepatocellular Carcinoma Using Gene Expression Pattern Analysis = Characterization of Cholangiocarcinoma-like Hepatocellular Carcinoma Using Gene Expression Pattern Analysis

다국어 초록 (Multilingual Abstract)

Aims: Hepatocelluar carcinoma (HCC), the most common primary liver cancer, shows very heterogeneous gene expression patterns compared with intrahepatic cholangiocarcinoma (CC). Recent studies revealed a subset of HCCs showing CC - like features in histopathologic and genomic levels. We tried to identify these overlapping tumors and to characterize this unique phenotype of HCC in clinical perspective. Methods: Genomic data were downloaded from The Cancer Genome Atlas (TCGA) on human HCC (n=374) and intrahepatic CC (n=30). Using uniquely expressed genes between HCC and intrahepatic CC, total 52 tumors (13.9%) were predicted as “CC-like” phenotype among HCCs (BRB array tool, BCCP model, P<0.001, cut off probability = 0.1). We found uniquely expressed 1,122 genes (CC signature set) between CC-like HCCs and the other HCCs ((P<0.0001, four fold changes). Using the CC signature set, we identified CC-like subgroup in other independent HCC cohorts. Results: Gene expression patterns of CC-like HCCs were significantly correlated with poor prognosis. They shared gene expressions with hepatic progenitor-origin tumors suggesting their origin might be shared with intrahepatic CC. The CC-like HCC also showed more aggressive gene expression patterns. Finally, CC-like HCCs showed significantly shorter overall survival than non-CC type in validation cohorts. Conclusions: Unique phenotype of HCC exists sharing similar gene expressions with CC and its genetic features are correlated with aggressive tumor biology.