Tumour-microenvironmental blood flow determines a metabolomic signature identifying lysophospholipids and resolvin D as biomarkers in endometrial cancer patients

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2017Author
Eldevik Fasmer, Kristine
Gatius Calderó, Sònia
Trovik, Jone
Krakstad, Camilla
Sol, Joaquim
Haldorsen, Ingfrid S.
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Eritja Sánchez, Núria;
Jové Font, Mariona;
Eldevik Fasmer, Kristine;
Gatius Calderó, Sònia;
Portero Otín, Manuel;
Trovik, Jone;
...
Matias-Guiu, Xavier.
(2017)
.
Tumour-microenvironmental blood flow determines a metabolomic signature identifying lysophospholipids and resolvin D as biomarkers in endometrial cancer patients.
Oncotarget, 2017, vol. 8, núm. 65, p, 109018-109026.
https://doi.org/10.18632/oncotarget.22558.
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Purpose: We aimed to study the potential influence of tumour blood flow –obtained from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)- in the metabolomic profiles of endometrial tumours.
Methods: Liquid chromatography coupled to mass spectrometry established the metabolomic profile of endometrial cancer lesions exhibiting high (n=12) or low (n=14) tumour blood flow at DCE-MRI. Univariate and multivariate statistics (ortho-PLS-DA, a random forest (RF) classifier and hierarchical clustering) and receiver operating characteristic (ROC) curves were used to establish a panel for potentially discriminating tumours with high versus low blood flow.
Results: Tumour blood flow is associated with specific metabolomic signatures. Ortho-PLS-DA and RF classifier resulted in well-defined clusters with an out-of-bag error lower than 8%. We found 28 statistically significant molecules (False Discovery Rate corrected p<0.05). Based on exact mass, retention time and isotopic distribution we identified 9 molecules including resolvin D and specific lysophospholipids associated with blood flow, and hence with a potentially regulatory role relevant in endometrial cancer.
Conclusions: Tumour flow parameters at DCE-MRI quantifying vascular tumour characteristics are reflected in corresponding metabolomics signatures and highlight disease mechanisms that may be targetable by novel therapies.
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Oncotarget, 2017, vol. 8, núm. 65, p, 109018-109026European research projects
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