Long and Very-Long-Chain Ceramides Correlate with A More Aggressive Behavior in Skull Base Chordoma Patients.

Background: Skull base chordomas are rare tumors arising from notochord. Sphingolipids analysis is a promising approach in molecular oncology, and it has never been applied in chordomas. Our aim is to investigate chordoma behavior and the role of ceramides.

Methods: Ceramides were extracted and evaluated by liquid chromatography and mass spectrometry in a cohort of patients with a skull base chordoma. Clinical data were also collected and correlated with ceramide levels. Linear regression and correlation analyses were conducted.

Results: Analyzing the association between ceramides level and MIB-1, total ceramides and dihydroceramides showed a strong association ( = 0.7257 and = 0.6733, respectively) with MIB-1 staining ( = 0.0033 and = 0.0083, respectively). Among the single ceramide species, Cer C24:1 ( = 0.8814, ≤ 0.0001), DHCer C24:1 ( = 0.8429, = 0.0002) and DHCer C18:0 ( = 0.9426, ≤ 0.0001) showed a significant correlation with MIB-1.

Conclusion: Our lipid analysis showed ceramides to be promising tumoral biomarkers in skull base chordomas. Long- and very-long-chain ceramides, such as Cer C24:1 and DHCer C24:1, may be related to a prolonged tumor survival and aggressiveness, and the understanding of their effective biological role will hopefully shed light on the mechanisms of chordoma radio-resistance, tendency to recur, and use of agents targeting ceramide metabolism.