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

Abstract

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 (r = 0.7257 and r = 0.6733, respectively) with MIB-1 staining (p = 0.0033 and p = 0.0083, respectively). Among the single ceramide species, Cer C24:1 (r = 0.8814, p ≤ 0.0001), DHCer C24:1 (r = 0.8429, p = 0.0002) and DHCer C18:0 (r = 0.9426, p ≤ 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.

Chordoma—Current Understanding and Modern Treatment Paradigms

“…Finally, an adenovirus serotype 5 (Ad5) vaccine encoding brachyury, carcinoembryonic antigen (CEA) and mucin-1, cell surface associated (MUC1) has been developed and is currently being tested in a Phase I clinical trial for patients with advanced cancers (NCT03384316, accessed on 31 January 2021). Finally, several studies have discussed pharmacological inhibition of the chordoma oncogene, TBXT (transcription factor brachyury), via inhibition of H3K27-demethylases as a promising novel therapy altering gene networks necessary for tumor survival [ 108 , 109 , 110 ].…”

Inhibition of Sphingolipid Synthesis as a Phenotype-Modifying Therapy in Cystic Fibrosis

“…Results were presented as the sum of the normalized intensity for each lipid within a class. Absolute sphingolipid determination was achieved using a targeted analysis by a LC-MS/MS system (Dionex 3000 UltiMate coupled to a tandem mass spectrometer AB Sciex 3200 QTRAP) as already described [58].…”

Ganglioside Composition Distinguishes Anaplastic Ganglioglioma Tumor Tissue from Peritumoral Brain Tissue: Complementary Mass Spectrometry and Thin-Layer Chromatography Evidence

“…In healthy brain tissue, CerS2 is transiently expressed in oligodendrocytes during active myelination [16]. Further on, a higher content of ceramides with long and very long fatty acid chains in skull base tumors was reported to correlate with more aggressive behavior of tumor cells [45]. On the other hand, a 70% reduction of C18-ceramide content was reported in GBM compared to normal brain tissue [46], while overexpressed CerS1 or exogenously added C18-ceramides showed inhibition of cell viability and induced apoptosis in cultured human glioma cells [47].…”