Expression profiling suggested a regulatory role of liver-enriched transcription factors in human hepatocellular carcinoma.

By using a cDNA array representing 14,000 cDNA clusters, we studied the expression profiles in paired clinical hepatocellular carcinoma (HCC) samples and the distal nontumorous liver tissues from the same patients. Despite the significant heterogeneity among the clinical samples, 72 genes (including 30 novel genes) were down-regulated and 84 genes (including 48 novel genes) were up-regulated in >50% of the cancer samples that were identified. The alterations in gene expression levels were confirmed by Northern blot and reverse-transcription PCR in all of 4 randomly selected genes. It was conspicuous that 21 of 38 hepatocarcinoma (HCC) down-regulated genes studied previously were reportedly regulated by a group of liver-enriched transcription factors (LETFs), and 12 of 36 HCC up-regulated genes studied previously were involved in protein translation. Reexamination of the cDNA array data further revealed that most of the genes known to be regulated by LETFs were down-regulated in at least a portion of the HCC samples. Among the LETFs, the expression level of CCAAT/enhancer-binding protein (C/EBP) alpha was down-regulated in cancer, whereas hepatocyte nuclear factor 1 (HNF-1), HNF-3beta, HNF-4alpha, and HNF-4gamma were up-regulated. The expression profiling thus suggested multiple regulatory pathways involved in HCC, especially that related to LETFs.