Cloning and characterization of a novel gene, DRH1, down-regulated in advanced human hepatocellular carcinoma

Few genes related to carcinogenesis and progression of hepatocellular carcinoma (HCC) have been identified to date. In the present study, we report the cloning and characterization of a novel gene, DRH1, which is frequently down-regulated in HCC. The full-length DRH1 clone contains an open reading frame of 1257 nucleotides encoding 419 amino acids. The deduced DRH1 protein shows 41% identity to VDUP1, expression of which is rapidly induced by 1,25-dihydroxyvitamin D₃The DRH1 gene was localized to chromosome 15, and DRH1 protein was mainly observed in the cytoplasm of transiently transfected cells. Real-time quantitative reverse transcription-PCR analysis showed that the expression level of DRH1 was reduced in 29 of 35 (83%) HCCs compared with corresponding noncancerous liver tissue. The average (mean ± SE) ratio of DRH1 expression level in tumor to corresponding noncancerous tissue was significantly different between well, moderately, and poorly differentiated HCCs (1.15 ± 0.23, 0.69 ± 0.10, and 0.19 ± 0.04, respectively) and between HCCs without and with vascular invasion (0.94 ± 0.16 and 0.46 ± 0.07, respectively). These results indicate that the down-regulation of DRH1 occurs not at an early stage but rather at a late stage of HCC progression. Although the function of DRH1 protein is still unknown, our findings suggest that DRH1 is related to the progression of HCC and may provide a new prognostic factor.