Plasma and ovarian tissue sphingolipids profiling in patients with advanced ovarian cancer.

ABSTRACT

PURPOSE: The role of lipids in carcinogenesis through induction of abnormal cell lines in the human body is currently undisputable. Based on the literature, bioactive sphingolipids play an essential role in the development and progression of cancer and are involved in the metastatic process. The aim of this study was to determine the concentration of selected sphingolipids in patients with advanced ovarian cancer (AOC, FIGO III/IV, high grade ovarian cancer). METHODS: Seventy-four patients with ovarian cancer were enrolled. Plasma concentrations of C16-Cer, C181-Cer and C18-Cer were assessed by LC/MS/MS. The content of tissue sphingolipids was measured using a UHPLC/MS/MS. RESULTS: Plasma concentration of 3 ceramides C16-Cer, C181-Cer and C18-Cer was significantly elevated in women with advanced ovarian cancer compared to control group (P=0.031; 0.022; 0.020; respectively). There were increases in concentration of 5 ceramides C16-Cer, C181-Cer, C18-Cer, C241-Cer, C24-Cer (P=0.025; 0.049; 0.032; 0.005; 0.013, respectively) and S1P (P=0.004) in ovarian tissue of women with advanced ovarian cancer compared to healthy individuals. Importantly, significantly higher risk of ovarian cancer when the plasma concentration of C16-Cer>311.88ng/100µl (AUC 0.76, P=0.0261); C181-Cer>4.75ng/100µl (AUC 0.77, P=0.0160) and C18-Cer>100.76ng/100µl (AUC0.77, P=0.0136) was noticed. CONCLUSIONS: Bioactive sphingolipids play an essential role in the development and progression of cancer and they also take part in the process of metastasizing. This study suggests that some sphingolipids can be used as potential biomarkers of advanced ovarian cancer and that they can play an important role in the pathogenesis of this disease.