Figure 4.

Levels of Trp and its metabolites are decreased in the sera of glioblastoma patients and associate with tumor volume. (A) Metabolite abundance of Trp, OH-Trp, FK, Kyn, AA, OH-Kyn, OH-AA in sera of age- and sex-matched controls (grey, n = 43) and glioblastoma patients (black, n = 43) relative to reference sample depicted as log2Ratio. Boxplots show median, 25^th and 75^th percentile, and whiskers maximal and minimal values. *P < 0.05, **P < 0.01, ***P < 0.001. n.s. not significant. (B) Volcano plot showing log₂FC of metabolite levels (x-axis) in patient (n = 43) versus control (n = 43) samples and corresponding -log₁₀ p values (y-axis). Metabolites highlighted in green were significantly decreased in patient versus control sera. (C) Same data depicted as in (B). Metabolite levels in patient versus control samples in log₂FC (y-axis) are ordered according to enzymatic steps away from Trp (x-axis). Metabolites highlighted in green were significantly decreased in patient versus control sera. (D) Forest plot depicting the association of metabolite levels in peripheral blood of patients (n = 43) with tumor volume based on MRI analyses. Mean ratio (MR) and 95% confidence intervals (CI) are shown. Green bars represent significant relationships. (E) Forest plot depicting the association of metabolite levels in peripheral blood of patients (n = 32) with overall survival. Mean ratio (MR) and 95% confidence intervals (CI) are shown. Green bar represents significant relationship. See also Table S15. Abbreviations: AA: anthranilic acid; AFMID: arylformamidase; CI: confidence interval; FC: fold change; FK: N-formylkynurenine; IDO1: indoleamine-2,3-dioxygenase 1; KMO: kynurenine 3-monooxygenase; Kyn: kynurenine; KYNU: kynureninase; MR: mean ratio; MRI: magnetic resonance imaging; OH-AA: hydroxy-anthranilic acid; OH-Kyn: hydroxy-kynurenine; OH-Trp: hydroxy-tryptophan; TDO2: tryptophan-2,3-dioxygenase; TPH1/2: tryptophan hydroxylase 1/2; Trp: tryptophan.