Genome-wide analysis of gene expression in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major risk factor associated with HCC is chronic hepatitis resulting from infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), but the molecular mechanisms of hepatocarcinogenesis still remain obscure. To elucidate the mechanisms of hepatocarcinogenesis, serial analysis of gene expression (SAGE) was performed in HBV-related HCC tissues (HCC-B), HCV-related HCC tissues (HCC-C), and associated noncancerous tissues. A total of 157,849 transcripts were generated, including 35,360 unique tags. Transcripts upregulated in the HCC-B library were those encoding HBV X protein, ESTs, osteonectin, and many unknown proteins. Transcripts upregulated in the HCC-C library were those encoding interferon gamma inducible proteins, oxidative stress-inducible proteins, glypican 3, and diubiquitin. Downregulation of genes associated with drug detoxification was observed in both HCC-B and HCC-C tissues. To evaluate the differential gene expression changes identified by SAGE in other HCCs, we prepared glass slides containing the sets of genes detected by SAGE, and performed cDNA microarray analysis on HCC-B and HCC-C tissues. Hierarchical clustering of these cDNA microarray data clearly distinguished HCC-B tissues from HCC-C tissues, validating the SAGE data. Thus, the combination of SAGE and cDNA microarray with human genome databases clarified differential gene expression patterns between HCC-B and HCC-C, and provided novel candidate genes to decipher the molecular mechanisms of carcinogenesis in chronic viral hepatitis.