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).