Expression Profiling Suggested A Regulatory Role Of Liver-enriched Transcription Factors In Human Hepatocellular Carcinoma

Employing a cDNA array representing 14,000 cDNA clusters, the expression profiles in paired clinical hepatocellular carcinoma (HCC) samples and the distal non-tumorous liver tissues from the same patients were studied. Despite the significant heterogeneity among the clinical samples, 72 genes (including 30 novel genes) down-regulated and 84 genes (including 48 novel genes) up-regulated in over 50% of the cancer samples were identified. The alterations in gene expression levels were confirmed by Northern blot and reverse-transcription polymerase-chain reaction in all of 4 randomly selected genes. It was conspicuous that 21 out of 38 HCC-down-regulated genes previously studied were reportedly regulated by a group of liver-enriched transcription factors (LETFs), and 12 out of 36 HCC-up-regulated genes previously studied 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. It is also demonstrated that among the LETFs, the expression level of CCAAT/enhancer-binding protein (C/EBP) alpha was down-regulated in cancer, while hepatocyte nuclear factor 1 (HNF1), HNF3 beta, HNF4 alpha and HNF4 gamma were up-regulated. The expression profiling thus suggested multiple regulatory pathways involved in HCC, especially that related to LETFs.