Plasma‐free amino acid profiles in dogs with hepatocellular carcinoma

Abstract

Background Metabolomic analysis using blood samples has been suggested to be useful for the early detection of cancer. Among metabolites, plasma‐free amino acid (PFAA) profiles are potential diagnostic biomarkers for several diseases including cancer. However, the relationship between PFAA concentrations and liver tumors in dogs remains unknown. Objective To determine the characteristics of PFAA profiles of dogs with hepatocellular carcinoma (HCC) and correlated clinical features. Animals Thirty‐four client‐owned dogs diagnosed with HCC (n = 26) and benign liver diseases (n = 8) and 11 age‐matched healthy dogs. Methods Prospective study using heparinized blood samples from fasted dogs. Plasma was deproteinized, and the concentrations of 21 amino acids were measured using an automated high‐performance liquid chromatography amino acid analyzer. Results Plasma glutamic acid concentrations were significantly different among groups ( P < .0024 after Bonferroni correction). Compared to healthy dogs, dogs with HCC and benign liver diseases had significantly higher concentrations of glutamic acid by post hoc analysis. However, no significant difference in the PFAA profiles of HCC and benign liver diseases were detected. In addition, preoperative and postoperative PFAA profiles of dogs with HCC were not significantly different. Conclusions and Clinical Importance Increased glutamic acid concentrations might play a role in the development or be a consequence of liver tumor formation. However, PFAA profiles of HCC could not be differentiated from those of benign lesions. In addition, glutamic acid concentrations did not change after surgical resection. These results indicate that PFAA profiles may not be useful biomarkers for detecting HCC in dogs.

Plasma amino acid profiles in dogs with closed extrahepatic portosystemic shunts are only partially improved 3 months after successful gradual attenuation

“…27 In a recent study in which amino acid profiles of dogs with congenital PSS, dogs with chronic hepatitis, and healthy dogs were analyzed, serum concentrations of BCAAs were significantly lower whereas serum concentrations of tyrosine and phenylalanine (both AAAs) were significantly higher, leading to a lower BCAA-to-AAA ratio in dogs with congenital PSS compared to healthy dogs and dogs with chronic hepatitis. 13 Although both tyrosine and phenylalanine concentrations were very high at diagnosis in our study, all BCAAs were at the lower end of the reference range reported in dogs, 18,19,[28][29][30] which is consistent with previous studies. [11][12][13] Although valine significantly increased after surgical attenuation, it remained within normal limits.…”

“…Liver diseases, however, are very diverse, and amino acid profiles found in dogs with different types of liver diseases vary markedly 18,28 . Dogs with focal liver masses have higher plasma glutamic acid concentrations compared to age‐matched healthy dogs regardless of whether the lesions were benign or hepatocellular carcinomas, and plasma glutamic acid concentrations were not significantly different 3 to 6 months after surgical resection of hepatocellular carcinomas 18 . Dogs with superficial necrolytic dermatitis (also called hepatocutaneous syndrome) have mean plasma amino concentrations that are significantly lower than those of dogs with acute and chronic hepatitis, most likely because of increased hepatic catabolism 28 .…”

“…Liver‐supportive diets are diets specifically manufactured for dogs with liver disease. Liver diseases, however, are very diverse, and amino acid profiles found in dogs with different types of liver diseases vary markedly 18,28 . Dogs with focal liver masses have higher plasma glutamic acid concentrations compared to age‐matched healthy dogs regardless of whether the lesions were benign or hepatocellular carcinomas, and plasma glutamic acid concentrations were not significantly different 3 to 6 months after surgical resection of hepatocellular carcinomas 18 .…”

“…An age‐ and size‐matched healthy control group could have been included to strengthen our findings. Blood amino acid concentrations in healthy dogs however vary among studies, with all studies describing relatively wide ranges 18,19,30 . In addition, differences in reported normal values can be explained by the fact that most studies only included a small number of apparently healthy dogs that received different types of food, and also by the fact that amino acids were analyzed using different laboratory techniques.…”

Metabolic profiling of 19 amino acids in triptolide-induced liver injured rats by gas chromatography-triple quadrupole mass spectrometry

“…Therefore, it is expected that the amino acids balance was broken in hepatic disease such as fatty liver disease, 7 cirrhosis 8 and liver cancer. 9 Triptolide (TP, its structure is shown in Figure 1), a cyclooxidized diterpene lactone, is a major active ingredient isolated from Tripterygium wilfordii Hook. F, 10 which has great potential in the treatment of rheumatoid arthritis 11 and cancer.…”