Significant differences in circulating metabolites between the PeALT and PnALT groups
To investigate the role of circulating metabolites in PeALT, plasma metabolomics was conducted, and 1051 metabolites were detected. Greater than 60% of the metabolites identified in the plasma belonged to the following six categories: amino acids and their metabolites (20.85%), benzene and its substituted derivatives (12.61%), organic acids and their derivatives (11.75%), heterocyclic compounds (10.62%), fatty acids (7.49%) and alcohol and amines (5.69%) (Figure 2A). OPLS-DA showed a clear separation in the metabolite profiles of the PeALT and PnALT groups (R2Y = 0.966, Q2 = 0.509, Figure 2B). The expression of 17 metabolites was significantly upregulated, whereas the expression of 23 metabolites was significantly downregulated in the PeALT group compared to that in the PnALT group (Figure 2C). KEGG pathway analysis revealed that the mTOR signaling pathway, drug metabolism-cytochrome P450, amino acid biosynthesis, D-amino acid metabolism, and central carbon metabolism in cancer were primarily enriched for the differential metabolites (Figure 2D). For further analysis, we focused on the top ten differential metabolites ranked by VIP, which reflected the level of influence of the metabolites. Levels of Lys-Ala-Leu-Glu (VIP = 4.49), 11-dehydrocorticosterone (VIP = 4.17), L-beta-phenylalanine (VIP = 3.65), N -acetyl-l-methionine (NALM) (VIP = 3.28), 3-methylxanthine (3-Mx) (VIP = 2.62), 7-methylxanthine (7-Mx) (VIP = 2.35), and Pro-His (VIP = 2.32) were significantly lower, while levels of Ser-Phe-Ala (VIP = 4.28), 3-methylhippuric acid (3-MA) (VIP = 3.04), and α-ketoglutaric acid (VIP = 2.82) were significantly higher in patients with PeALT than in patients with PnALT (Figure 2E and 2F).