Arginase-1 and glypican-3 gene expression studies confirmed that the tumor samples used in our study originate from HCC livers but not non-hepatocellular tumors. mRNA and protein expression of PPM1A and CYP3A4 was found to be significantly repressed in the tumor liver tissues compared to the matched non-tumor liver tissues.
This report represents, to the best of our knowledge, the first case of biopsy-proven hepatocellular carcinoma in an individual with arginase 1 deficiency.
This finding is of fundamental clinical importance in view of previous studies that have shown arginase-1 to be always positive in well-differentiated HCC.
In conclusion, branched chain ISH performed on manual and automated mode is a robust assay for detecting albumin with sensitivity for poorly differentiated HCCs superior to Arginase-1 and Hep Par 1.
Arg-1 is a more sensitive and better specific marker for HCC compared with HepPar-1 and AFP, indicating that Arg-1 can be easily applied in distinguishing HCC from metastatic tumors.
In vitro cytotoxicity experiments verified that the Co(2+)-substituted human Arg I displays an approximately 12- to 15-fold lower IC(50) value for the killing of human hepatocellular carcinoma and melanoma cell lines and thus constitutes a promising new candidate for the treatment of l-Arg auxotrophic tumors.
Arginase 1 expression was elevated in more than 75% of HCV infected liver samples compared with paired HCC from the same patients (>33% positive) and to uninfected liver tissues (0% positive).