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

View/ Open
Issue date
2017Author
Eldevik Fasmer, Kristine
Gatius Calderó, Sònia
Trovik, Jone
Krakstad, Camilla
Sol, Joaquim
Haldorsen, Ingfrid S.
Suggested citation
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.
Metadata
Show full item recordAbstract
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.
Is part of
Oncotarget, 2017, vol. 8, núm. 65, p, 109018-109026European research projects
Collections
The following license files are associated with this item:
Related items
Showing items related by title, author, creator and subject.
-
Metabotyping human endometrioid endometrial adenocarcinoma reveals an implication of endocannabinoid metabolism
Jové Font, Mariona; Gatius Calderó, Sònia; Yeramian Hakim, Andree; Portero Otín, Manuel; Eritja Sánchez, Núria; Santacana Espasa, Maria; Colás, Eva; Ruiz, M.; Pamplona Gras, Reinald; Matias-Guiu, Xavier (Impact Journals, 2016)Metabolomics, an essential technique in precision medicine, contributes to the molecular fingerprinting of tumours, further helping to understand their pathogenesis. In this work, using a LC-ESI-QTOF-MS/MS platform, we ... -
Autophagy orchestrates adaptive responses to targeted therapy in endometrial cancer
Eritja Sánchez, Núria; Chen, Bo-Juen; Rodríguez Barrueco, Ruth; Santacana Espasa, Maria; Gatius Calderó, Sònia; Vidal, August; Martí, Maria Dolores; Ponce, Jordi; Bergadà Bertran, Laura; Yeramian Hakim, Andree; Encinas Martín, Mario; Ribera i Calvet, Joan; Reventós, Jaume; Boyd, Jeff; Villanueva, Alberto; Matias-Guiu, Xavier; Dolcet Roca, Xavier; Llobet Navàs, David (Taylor & Francis, 2017)Targeted therapies in endometrial cancer (EC) using kinase inhibitors rarely result in complete tumor remission and are frequently challenged by the appearance of refractory cell clones, eventually resulting in disease ... -
An inducible knockout mouse to model the cellautonomous role of PTEN in initiating endometrial, prostate and thyroid neoplasias
Mirantes Barbeito, Cristina; Eritja Sánchez, Núria; Dosil, Maria Alba; Santacana Espasa, Maria; Pallares, Judit; Gatius Calderó, Sònia; Bergadà Bertran, Laura; Maiques Carlos, Oscar; Matias-Guiu, Xavier; Dolcet Roca, Xavier (Company of Biologists, 2013)PTEN is one of the most frequently mutated tumor suppressor genes in human cancers. The role of PTEN in carcinogenesis has been validated by knockout mouse models. PTEN heterozygous mice develop neoplasms in multiple ...