Source State Key Laboratory for Liver Research and Department of Pathology, Li Ka Shing Faculty Medicine, The University of Hong Kong, Hong Kong. jackwong@pathology.hku.hk.

Hepatocellular carcinoma (HCC) is a prevalent cancer with an extremely high mortality rate, attributed to HCC metastasis which is the major cause of tumor recurrence and organ failure. Presence of tumor thrombi in the portal veins (venous metastases) is a clinicopathological feature of metastatic HCCs. In this study, we analyzed the microRNA (miRNA) expression profiles of non-tumorous livers, primary HCCs, and venous metastases in the same livers from 20 HCC patients by low density microarray (LDA) and identified the precise alterations of miRNA expression from non-tumorous livers to primary HCCs and venous metastases globally. By unsupervised clustering analysis, non-tumorous livers were distinctly segregated from primary HCCs and venous metastases, whereas no discernible difference in the expression pattern could be found between primary HCCs and venous metastases. However, a marked global reduction of miRNA expression levels was detected in venous metastases, as compared with primary HCCs. These data suggest that miRNA deregulation is an early event in liver carcinogenesis and the later global miRNA down-regulation aggravates the pre-existing miRNA deregulation to further promote HCC metastasis. Our study has enriched the current understanding of the deregulation of miRNAs in HCC progression and highlighted the sequential and distinctive alterations of miRNA expression in primary HCC and venous metastasis formation.