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

ABSTRACT

INTRODUCTION: Due 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 METHODS: A 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 C140-Cer, C160-Cer, C181-Cer, C180-Cer, C200-Cer, C220-Cer, C241-Cer and C240-Cer were assessed by LC/MS/MS. RESULTS: Plasma concentrations of C16-Cer, C181-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 C181-Cer was significantly higher in erythrocytes of women with advanced serous cancer compared to the control group (p = 0.027). Plasma C16-Cer and C181-Cer levels and erythrocyte C181-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). CONCLUSIONS: Plasma concentrations of C16, C18.1 and C18 correlated with the progression of ovarian cancer (FIGO staging and grading). Plasma levels of C16-Cer and C181-Cer and erythrocyte C181-Cer levels could be used to distinguish patients with advanced serous ovarian cancer.