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 eval...
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doaj-0a19082388d84ab1b860d3b9dfdfccef2020-11-24T21:58:33ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-09-012018448010.3390/ijms20184480ijms20184480Long and Very-Long-Chain Ceramides Correlate with A More Aggressive Behavior in Skull Base Chordoma PatientsEmanuele La Corte0Michele Dei Cas1Alberto Raggi2Monica Patanè3Morgan Broggi4Silvia Schiavolin5Chiara Calatozzolo6Bianca Pollo7Carlotta Pipolo8Maria Grazia Bruzzone9Giuseppe Campisi10Rita Paroni11Riccardo Ghidoni12Paolo Ferroli13PhD School in Molecular and Translational Medicine, Department of Health Sciences, University of Milan, 20142 Milan, ItalyPhD School in Molecular and Translational Medicine, Department of Health Sciences, University of Milan, 20142 Milan, ItalyNeurology, Public Health and Disability Unit, Fondazione IRCCS Istituto Neurologico “Carlo Besta”, 20133 Milan, ItalyNeuropathology Unit, Fondazione IRCCS Istituto Neurologico “Carlo Besta”, 20133 Milan, ItalyDepartment of Neurosurgery, Fondazione IRCCS Istituto Neurologico “Carlo Besta”, 20133 Milan, ItalyNeurology, Public Health and Disability Unit, Fondazione IRCCS Istituto Neurologico “Carlo Besta”, 20133 Milan, ItalyNeuropathology Unit, Fondazione IRCCS Istituto Neurologico “Carlo Besta”, 20133 Milan, ItalyNeuropathology Unit, Fondazione IRCCS Istituto Neurologico “Carlo Besta”, 20133 Milan, ItalyOtolaryngology Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, 20142 Milan, ItalyNeuroradiology Department, Fondazione IRCCS Istituto Neurologico “Carlo Besta”, 20133 Milan, ItalyPhD School in Molecular and Translational Medicine, Department of Health Sciences, University of Milan, 20142 Milan, ItalyClinical Biochemistry and Mass Spectrometry Laboratory, Department of Health Sciences, University of Milan, 20142 Milan, ItalyPhD School in Molecular and Translational Medicine, Department of Health Sciences, University of Milan, 20142 Milan, ItalyDepartment of Neurosurgery, Fondazione IRCCS Istituto Neurologico “Carlo Besta”, 20133 Milan, ItalyBackground: 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 (<i>r</i> = 0.7257 and <i>r</i> = 0.6733, respectively) with MIB-1 staining (<i>p</i> = 0.0033 and <i>p</i> = 0.0083, respectively). Among the single ceramide species, Cer C24:1 (<i>r</i> = 0.8814, <i>p</i> ≤ 0.0001), DHCer C24:1 (<i>r</i> = 0.8429, <i>p</i> = 0.0002) and DHCer C18:0 (<i>r</i> = 0.9426, <i>p</i> ≤ 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.https://www.mdpi.com/1422-0067/20/18/4480cancerceramideschordomadihydroceramideslipid targetsskull basesphingolipids |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Emanuele La Corte Michele Dei Cas Alberto Raggi Monica Patanè Morgan Broggi Silvia Schiavolin Chiara Calatozzolo Bianca Pollo Carlotta Pipolo Maria Grazia Bruzzone Giuseppe Campisi Rita Paroni Riccardo Ghidoni Paolo Ferroli |
spellingShingle |
Emanuele La Corte Michele Dei Cas Alberto Raggi Monica Patanè Morgan Broggi Silvia Schiavolin Chiara Calatozzolo Bianca Pollo Carlotta Pipolo Maria Grazia Bruzzone Giuseppe Campisi Rita Paroni Riccardo Ghidoni Paolo Ferroli Long and Very-Long-Chain Ceramides Correlate with A More Aggressive Behavior in Skull Base Chordoma Patients International Journal of Molecular Sciences cancer ceramides chordoma dihydroceramides lipid targets skull base sphingolipids |
author_facet |
Emanuele La Corte Michele Dei Cas Alberto Raggi Monica Patanè Morgan Broggi Silvia Schiavolin Chiara Calatozzolo Bianca Pollo Carlotta Pipolo Maria Grazia Bruzzone Giuseppe Campisi Rita Paroni Riccardo Ghidoni Paolo Ferroli |
author_sort |
Emanuele La Corte |
title |
Long and Very-Long-Chain Ceramides Correlate with A More Aggressive Behavior in Skull Base Chordoma Patients |
title_short |
Long and Very-Long-Chain Ceramides Correlate with A More Aggressive Behavior in Skull Base Chordoma Patients |
title_full |
Long and Very-Long-Chain Ceramides Correlate with A More Aggressive Behavior in Skull Base Chordoma Patients |
title_fullStr |
Long and Very-Long-Chain Ceramides Correlate with A More Aggressive Behavior in Skull Base Chordoma Patients |
title_full_unstemmed |
Long and Very-Long-Chain Ceramides Correlate with A More Aggressive Behavior in Skull Base Chordoma Patients |
title_sort |
long and very-long-chain ceramides correlate with a more aggressive behavior in skull base chordoma patients |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-09-01 |
description |
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 (<i>r</i> = 0.7257 and <i>r</i> = 0.6733, respectively) with MIB-1 staining (<i>p</i> = 0.0033 and <i>p</i> = 0.0083, respectively). Among the single ceramide species, Cer C24:1 (<i>r</i> = 0.8814, <i>p</i> ≤ 0.0001), DHCer C24:1 (<i>r</i> = 0.8429, <i>p</i> = 0.0002) and DHCer C18:0 (<i>r</i> = 0.9426, <i>p</i> ≤ 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. |
topic |
cancer ceramides chordoma dihydroceramides lipid targets skull base sphingolipids |
url |
https://www.mdpi.com/1422-0067/20/18/4480 |
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