Fig. 8: Decreased levels of C1-related metabolites and protein malonylation in blood samples from severe cachexia mouse models and advanced gastric cancer cachexia patients.
From: Decreased liver B vitamin-related enzymes as a metabolic hallmark of cancer cachexia
a C1- and NAD- related metabolites commonly altered in blood samples of CRCA mice and clinical cachexia patients (Welch’s 2-sided t-test, P-value < 0.05). These graphs show levels of betaine, serine (Ser), threonine (Thr), choline, guanidinoacetate (GAA), and tryptophan (Trp) with respect to controls. GC, gastric cancer. Cachexia GC, N = 25 patients; MEWO, N = 6 mice; LNCA, N = 10 mice; SEKI, N = 8 mice; CRCA, N = 13 mice; STRV, N = 8 mice. Welch’s 2-sided t-test presented only for cachexia GC, SEKI, and CRCA; *P < 0.05, **P < 0.01, ***P < 0.001. Non-adjusted P-values (Welch’s 2-sided t-test); Cachexia GC, betaine (0.0145), Ser (0.0135), Thr (0.00690), choline (5.32 × 10−5), GAA (0.000254), Trp (1.13 × 10−10); SEKI, betaine (0.118), Ser (0.00492), Thr (0.749), choline (0.184), GAA (2.51 × 10−5), Trp (5.99 × 10−5); CRCA, betaine (7.65 × 10−6), Ser (0.00122), Thr (0.000757), choline (0.0324), GAA (1.1 × 10−5), Trp (6.88 × 10−17); Boxplot style, the middle line (median), the upper hinge (Q3, the third quantile), the lower hinge (Q1, the first quantile), the upper whisker (1.5 × (Q3 − Q1)), the lower whisker (1.5 × (Q3 – Q1)). b Integrated fold changes of blood metabolites from early and advanced gastric cancer patients with respect to those from reference samples. GPS 0, N = 20 patients; GPS 1, N = 10; patients; GPS 2, N = 27 patients. Dashed lines, linear model; gray area, 95% confidence interval. P-values by Jonckheere’s trend test (one-sided) for GPS order. c, Percentage of liver-derived proteins in human plasma proteome data weighted by protein abundance (3461 human plasma proteins). d Volcano plots of malonyl-K (malK) and acetyl-K (aceK) data for blood proteins in SEKI and CRCA mice. Blue points, liver-derived proteins; gray points, other proteins. SEKI, N = 3 mice; CRCA, N = 3 mice. Adjusted FC, fold changes adjusted by total protein fold changes. Horizontal dashed lines, P = 0.05 (Welch’s 2-sided t-test). e Box plots with horizontally jittered points for fold-changes of malK and aceK peptides from liver-derived blood proteins. Change values were calculated from SEKI mouse datasets (N = 3 mice) with control nude mice (N = 3 mice), CRCA mice (N = 3 mice) with control C57BL/6N mice (N = 3 mice), and gastric cancer cachexia patients (N = 4 patients) with control early gastric cancer patients without cachexia (N = 6 patients). Percentage values for BW (body weight) indicate each patient’s weight changes between blood collection timepoints and ~6 months before. Adjusted FC, fold changes adjusted by fold changes of total protein levels. APPs, acute-phase proteins. Note that only proteins with an adjusted FC >0.03 and <32 and a P-value (Welch’s 2-sided t-test) <0.05 are presented. Boxplot style, the middle line (median), the upper hinge (Q3, the third quantile), the lower hinge (Q1, the first quantile), the upper whisker (1.5 × (Q3 − Q1)), the lower whisker (1.5 × (Q3 – Q1)). f Schematic of cachexia-associated metabolic changes in the liver and blood. Source data are provided as a Source Data file.
