Arginase-1 and P-glycoprotein are downregulated in canine hepatocellular carcinoma

J Vet Sci. 2021 Sep;22(5):e61. doi: 10.4142/jvs.2021.22.e61. Epub 2021 Jul 12.

Abstract

Background: Hepatocellular carcinoma is the most common primary hepatic malignancy in humans and dogs. Several differentially expressed molecules have been studied and reported in human hepatocellular carcinoma and non-neoplastic liver lesions. However, studies on the features of canine hepatocellular carcinoma are limited, especially related to the differential characteristics of neoplastic and non-neoplastic lesions.

Objectives: The study's objective was 1) to examine and evaluate the expression of arginase-1, P-glycoprotein, and cytokeratin 19 in canine liver tissues and 2) to investigate the differential features of hepatocellular carcinomas, liver tissue with non-neoplastic lesions, and paracancerous liver tissues in dogs.

Methods: The expression levels of three markers underwent immunohistochemical analysis in 40 non-neoplastic liver tissues, 32 hepatocellular carcinoma tissues, and 11 paracancerous liver tissues. Scoring of each marker was performed semi-quantitatively.

Results: Arginase-1 and P-glycoprotein were significantly downregulated in hepatocellular carcinoma, compared with hepatic tissues with non-neoplastic diseases (p < 0.001). Expression levels of arginase-1 and P-glycoprotein were also significantly lower in hepatocellular carcinoma than in paracancerous liver tissues (arginase-1, p = 0.0195; P-glycoprotein, p = 0.047). Few cytokeratin 19-positive hepatocytes were detected and only in one hepatocellular carcinoma and one cirrhotic liver sample.

Conclusions: The results of this study suggest that downregulation of arginase-1 and P-glycoprotein is a feature of canine hepatocellular carcinoma; thus, those markers are potential candidates for use in differentiating hepatocellular carcinomas from non-neoplastic liver lesions in dogs.

Keywords: Arginase; P-glycoprotein; dog; hepatocellular carcinoma; liver.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Animals
  • Arginase / genetics*
  • Arginase / metabolism
  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / veterinary*
  • Dog Diseases / etiology
  • Dog Diseases / metabolism*
  • Dogs
  • Down-Regulation*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Arginase