Blood bioactive sphingolipids in patients with advanced serous epithelial ovarian cancer – mass spectrometry analysis

Abstract

IntroductionDue to the lack of highly specific and sensitive methods for diagnosing ovarian cancer at advanced stages (according to the International Federation of Gynecology and Obstetrics (FIGO) classification stage III–IV), new noninvasive biomarkers are urgently needed. This study aims to investigate how the levels of plasma bioactive sphingolipids (ceramides, sphingosine-1-phosphate, sphingosine and sphinganine) are altered in serum, erythrocytes and platelets of patients with advanced serous ovarian cancer.Material and methodsA total of 135 patients with advanced serous ovarian cancer and 159 women with normal ovarian morphology were enrolled. Plasma levels of sphingosine, sphingosine-1-phosphate, sphinganine, ceramide C14:0-Cer, C16:0-Cer, C18:1-Cer, C18:0-Cer, C20:0-Cer, C22:0-Cer, C24:1-Cer and C24:0-Cer were assessed by LC/MS/MS.ResultsPlasma concentrations of C16-Cer, C18:1-Cer and C18-Cer were significantly higher in the advanced ovarian cancer group than in the control group (1.5-fold, p = 0.021; 1.8-fold, p = 0.036 and 1.5-fold, p = 0.031, respectively). Plasma concentration of C18:1-Cer was significantly higher in erythrocytes of women with advanced serous cancer compared to the control group (p = 0.027). Plasma C16-Cer and C18:1-Cer levels and erythrocyte C18:1-Cer levels were able to distinguish patients with moderate/severe serous ovarian cancer from patients with mild ovarian cancer (AUC: 0.86, 0.898, 0.795, respectively). Plasma concentrations of C16, C18.1 and C18 significantly correlated with FIGO staging (p = 0.001, p = 0.024 and p = 0.005), and grading (p = 0.021, p = 0.021 and p = 0.033).ConclusionsPlasma concentrations of C16, C18.1 and C18 correlated with the progression of ovarian cancer (FIGO staging and grading). Plasma levels of C16-Cer and C18:1-Cer and erythrocyte C18:1-Cer levels could be used to distinguish patients with advanced serous ovarian cancer.