Serum Amino Acid Profiles Predict the Development of Hepatocellular Carcinoma in Patients with Chronic HBV Infection

Abstract

Background: The study aimed to find out the alterations in serum amino acid (AA) profiles and to detect their relationship with carcinoma formation. Methods: Targeted metabolomics based on ultraperformance liquid chromatography triple quadrupole mass spectrometry to quantitatively analyze serum AA levels in 136 hepatitis B (CHB) patients and 93 hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients. Results: It was shown that decreased serum levels of leucine, lysine, threonine, tryptophan, valine, serotonin, and taurine were observed in more HCC patients than CHB patients, but the serum phenylalanine level was increased. Serum valine and serotonin were lower in Class C than Class A and Class B in HCC patients. Accompanied with the higher score of Model for End-Stage Liver Disease, serum phenylalanine was increased not only in CHB patients but also in HCC patients. The serum level of phenylalanine increased in the decompensated stage more than in the compensated stage, while serum leucine and serotonin significantly decreased. Serum serotonin still had significant differences between CHB and HCC both in the HBV desoxyribonucleic acid (HBV-DNA) negative group and in the HBV-DNA positive group. Furthermore, it was shown that the tryptophan ratio, branched-chain amino acids (BCAA)/aromatic amino acids ratio, BCAAs/tyrosine ratio, Fischer’s ratio, and serotonin-to-tryptophan ratio significantly decreased, while the tyrosine ratio and the kynurenine-to-tryptophan ratio increased in HCC patients more than those in CHB. Conclusions: A distinct metabolite signature of some specific serum amino acids was found between CHB and HCC patients, which may help predict the development of HCC at an early stage.

Causal associations of BAFF-R on IgD+ CD24- B cell immune cell trait with hepatocellular carcinoma and the mediating role of phenylacetylglutamate levels: a Mendelian randomization study

“…The tyrosine metabolism-related genes and intermediary product in the phenylalanine metabolism pathway were con rmed to be involved in HCC (32)(33)(34). Furthermore, the serum concentration of phenylalanine and tyrosine were both signi cantly increased in HCC patients (35,36). The literature have indicated the presence of an interactive dialogue between tyrosine metabolism and the tumor immune microenvironment (37,38).…”

Identification of CD8+ T-cell exhaustion signatures for prognosis in HBV-related hepatocellular carcinoma patients by integrated analysis of single-cell and bulk RNA-sequencing

“…Furthermore, high tyrosine levels in HCC patients are closely associated with poor prognosis [ 35 ]. Metabolomic studies have demonstrated that HBV-positive HCC patients exhibit significantly higher serum tyrosine levels than HBV-negative HCC patients [ 36 , 37 ]. Research on tumor immunotherapy has shown that consuming a diet low in tyrosine and phenylalanine can improve the body’s anti-tumor immune response [ 38 ].…”

Evaluation of Amino Acids Profile as Non-Invasive Biomarkers of Hepatocellular Carcinoma in Egyptians

“…In contrast, the level of phenylalanine, one of the AAAs, was significantly increased. Scatter diagrams showed differences in these amino acids between CHB and HCC patients and proposed that the increase in phenylalanine level due to seriously hepatic impairment in HCC patients versus CHB patients because of phenylalanine is mainly metabolized in the liver [33].…”