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.
Eritja, N., Jové, M., Fasmer, K. E., Gatius, S., Portero-Otin, M., Trovik, J., … Matias-Guiu, X. (2017). Tumour-microenvironmental blood flow determines a metabolomic signature identifying lysophospholipids and resolvin D as biomarkers in endometrial cancer patients. Oncotarget, 8(65). https://doi.org/10.18632/oncotarget.22558