Expression of argininosuccinate synthetase in patients with hepatocellular carcinoma

Background and Aim Arginine is a nonessential amino acid for humans and mice because it can be synthesized from citrulline by argininosuccinate synthetase (ASS) and argininosuccinate lyase. Hepatocellular carcinoma (HCC) is believed to be auxotrophic for arginine through the lack of expression of ASS. However, there are also some ASS-positive HCC cells. Therefore, the aim of this article was to study the levels of arginine and the expression of ASS in patients with HCC. Methods Thirty patients with HCC who had undergone HCC surgery were enrolled in the study. Serum arginine levels were determined with an automatic amino acid analyzer. ASS expression was examined by Western blot and immunohistochemistry. Methylation specific polymerase chain reaction and methylation sequencing were performed to detect the methylation of DNA encoding ASS. Results There was a decrease of arginine in HCC patients compared with that of healthy control. High expression of ASS was found in the adjacent tissues by Western blot and immunohistochemistry. Little ASS expression was found in most HCC tissues, but there were also some HCC tissues that expressed low levels of ASS. Methylation of the DNA encoding ASS was obviously higher in HCC tissues than that in paired adjacent tissues. Conclusions ASS expression is decreased significantly in HCC tissues. The downregulation of arginine and ASS expression may be a self-defense action of the body against malignant tumors, and the decreased arginine and ASS levels in HCC patients are an advantage for the arginine deiminase treatment.