Discrimination and clinical value of plasma metabolomic profiles in multidrug resistant epithelial ovarian cancer

Abstract

Objective: To explore the alteration of plasma metabolomic profiles, screen the new serum markers of multidrug resistant epithelial ovarian cancer (EOC), and investigate the mechanism. Methods: The serum of 132 cases with cisplatin-resistant EOC, cisplatin-sensitive EOC, benign ovarian cyst and healthy donors were collected. Differentially plasma metabolic profiles were identified by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The significantly different metabolites of each group were screened by using principal component analysis. Then compounds that played a key role in cisplatin resistance were identified by using nuclear magnetic resonance (NMR). The relationships between these compounds and clinical characteristics and prognosis were analyzed. Results: LC-MS/MS identified 25 800 metabolic compounds. According to the descending dimension algorithm by principal component analysis, six compounds which were the biggest contributor to grouping were identified. The identified results of NMR showed that the serum level of C16 Sphinganine was lower while Dodemorph was higher in the EOC than those of the normal control. Compared to the cisplatin sensitive group, cisplatin resistant group exhibited a specific metabolic trait characterized by upregulation of 1-Monopalmitin, Ricinoleic acid methyl ester, Polyoxyethylene (600) mono-ricinoleate/Glycidyl stearate and downregulation of Calycanthidine. The four components were all associated with fatty acid metabolism, and the combinational diagnostic sensitivity of these biomarkers for cisplatin-resistance was 86.50% and the specificity was 81.80%, the area of receiver operating characteristic (ROC) curve was 0.93. Conclusions: The metabolic signatures of normal control, benign ovarian cyst, cisplatin sensitivity and cisplatin resistance can be clearly separated from each other by LC-MS/MS technology.The combinational four biomarkers including Calycanthidine, 1-Monopalmitin, Ricinoleic acid methl ester and Polyoxyethylene (600) mono-ricinoleate/Glycidyl stearate are more sensitive and specific for the diagnosis of cisplatin resistant EOC, and may provide the potentially predict markers of chemotherapeutic response in metabolic level. The fatty acid metabolism may participate in the cisplatin resistant progression of EOC.