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Title:
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Tumour-microenvironmental blood flow determines a metabolomic signature identifying lysophospholipids and resolvin D as biomarkers in endometrial cancer patients
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Author:
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Eritja Sánchez, Núria; Jové Font, Mariona; Eldevik Fasmer, Kristine; Gatius Calderó, Sònia; Portero Otín, Manuel; Trovik, Jone; Krakstad, Camilla; Sol, Joaquim; Pamplona Gras, Reinald; Haldorsen, Ingfrid S.; Matias-Guiu, Xavier
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Notes:
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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.
Supported by grants, PI13/01701 and PI16/00692 from Fondo de Investigaciones Sanitarias del Instituto de Salud Carlos III cofinanciado por Fondo Europeo de Desarrollo Regional (FEDER) (“Una manera de hacer Europa”), Red Temática de investigación en Cáncer RD12/0036/0013 and Red de Oncología (CIBERONC-ONCG33/2017) and the Department of Health from the Generalitat of Catalonia (SLT002/16/00250). Grups consolidats de la Generalitat de Catalunya (2009SGR794 and 2014SGR168), Fundació La Marató de TV3 (2/C2013), Grupos estables AECC, Plataforma de Biobancos ISCIII (PT13/0010/0014) and ENITEC NETWORK. NE holds a postdoctoral fellowship from Generalitat de Catalunya (SLT002/16/00274). |
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Subject(s):
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-Endometrial cancer
-DCE-MRI
-Blood flow
-Metabolomic analysis |
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Rights:
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cc-by (c) Eritja et al., 2017
http://creativecommons.org/licenses/by/4.0/
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Document type:
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article
publishedVersion |
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Published by:
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Impact Journals
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