[HTML][HTML] Tumour-microenvironmental blood flow determines a metabolomic signature identifying lysophospholipids and resolvin D as biomarkers in endometrial …

N Eritja, M Jové, KE Fasmer, S Gatius, M Portero-Otin… - Oncotarget, 2017 - ncbi.nlm.nih.gov
N Eritja, M Jové, KE Fasmer, S Gatius, M Portero-Otin, J Trovik, C Krakstad, J Sol…
Oncotarget, 2017ncbi.nlm.nih.gov
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 …
Abstract
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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