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 exp ression profiles in paired clinical hepatocellular carcinoma (HCC) samples and the distal nontumorous Liver tissues from the same patients. Despite th e 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 consp icuous that 21 of 38 hepatocarcinoma (HCC) down-regulated genes studied pre viously were reportedly regulated by a group of liver-enriched transcriptio n factors (LETFs), and 12 of 36 HCC up-regulated genes studied previously w ere involved in protein translation. Reexamination of the cDNA array data f urther 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, t he expression level of CCAAT/enhancer-binding protein (C/EBP) alpha was dow n-regulated in cancer, whereas hepatocyte nuclear factor 1 (HNF-1), HNF-3 b eta, HNF-4 alpha, and HNF-4 gamma were up-regulated. The expression profili ng thus suggested multiple regulatory pathways involved in HCC, especially that related to LETFs.