Hep Par 1 Antigen (Cps1) Expression In Liver Cancer Is Regulated By Dna Methylation

Hep Par 1 antibody is widely used in surgical pathology practice. We have previously identified the antigen of this antibody as " carbamoyl phosphate synthetase 1 (CPS1), a liver‐specific, rate‐limiting enzyme in the Urea Cycle. Expression of CPS1 appears to be related to the differentiation state of hepatocellular carcinoma (HCC). The objective of our study is to determine the expression profile of CPS1 in liver cancer and to elucidate the molecular mechanism of the gene expression control in carcinogenesis. Using human liver cancer tissues, primary hepatocyte culture, and liver cancer cell lines, we found that HCC cell lines and poorly differentiated HCC did not express CPS1, and all twenty HCC tissues examined expressed low levels of CPS. Primary hepatocyte culture had overt CPS1 expression. We also found that 5‐azacytidine (AZA) treatment restored CPS1 expression in the three cancer cell lines, Huh7, Huh7.5, and LH86, indicating the role of DNA methylation in CPS1 expression control. We then examined the DNA methylation status of CpG regions in the CPS1 promoter. Our data clearly show that the CpG regions are hypermethylated in liver cancer cells. Our study indicates that CPS1 is suppressed by DNA methylation in cancer cells, a reflection of aberrant DNA methylation in liver cancer. We suggest that CPS1 may play a role in carcinogenesis, and its methylation status may be a useful biomarker for liver cancer.