Masaaki Oka

15 – Hepatocellular Carcinoma of Differential Viral Origin: Analysis by Oligonucleotide Microarray

The hepatitis B virus (HBV) strain is a partially double-stranded hepatotropic DNA virus belonging to the Hepadnaviridae family. It is generally accepted that the majority of HBV-related hepatocellular carcinoma (HCCs) contain the HBV DNA sequence integrated into the cellular chromosomal DNA, suggesting that viral integration may act as a random insertional mutagen, which leads to or contributes to secondary chromosomal rearrangements, such as inversions, translocations, or deletions. DNA microarray analysis is a state-of-the art, high-throughput technology that has ushered in a new era in the medical sciences. Many studies using this technology have detected pathogenesis-related genes in human HCCs. Distinct differences in gene expression patterns between HBV positive HCCs and hepatocellular virus (HCV)-positive HCCs have been identified. Recently, the gene expression profiles of HBV- and HCV-negative HCCs (non-B, non-C HCCs) with similar microarrays are analyzed, and the gene expression patterns of non-B, non-C HCCs with those of B- and C-type HCCs using a supervised learning method are compared. The results of these studies provide a framework to better understand the pathogenesis of HCCs of differential viral origins and to provide additional markers and molecular targets for the diagnosis and treatment of each type of HCC. The molecular basis of HCCs of differential viral origins is discussed with respect to molecular profiling.