PMC

(A) PCA plot showing the 1^st and 2^nd principal components and separation of the patients with and without malignant tumors. (B) Summary of the global metabolic differences observed in ovarian cancer patient serum samples. (C) Volcano plot illustrating the most significantly altered metabolites in the serum of patients with malignant tumors. For clarity, only main peaks are shown, and the unidentified compounds and sugars/sugar alcohols are omitted from the figure. (D) Concentration of the most significantly altered metabolites and CA-125 in patients without malignant tumors as well as in patients with malignant tumors that were either completely or incompletely removed during the surgery.

Higher concentrations of (A) 2,4-dihydroxybutyric, 3,4-dihydroxybutyric and adipic acids in serum were all associated with poor overall survival of the patients. In contrast, (B) CA-125 did not show association with the survival. (C) Illustration of the pathway and metabolites that are altered due to loss of SSADH activity. Arrow means that the metabolite was upregulated in patients with malignant tumors, and circle that high concentration was associated with worse overall survival. The data for GABA was obtained from (). The accumulation of adipic acid has been associated with SSADH deficiency, but the mechanism leading to the higher concentration of this metabolite has not been elucidated, and therefore the arrows in this figure refer only to a hypothetical mechanism. (D) Low expression and loss in copy number of ALDH5A1 in tumors were associated with poor survival in TCGA data and. (E) The association of low expression of ALDH5A1 in tumors to poor survival was replicated also in publicly available survival analysis tool of ovarian serous carcinoma patients (n=1137).