Targeted UPLC-MS Metabolic Analysis of Human Faeces Reveals Novel Low-Invasive Candidate Markers for Colorectal Cancer
Low invasive tests with high sensitivity for colorectal cancer and advanced precancerous lesions will increase adherence rates, and improve clinical outcomes. We have performed an ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-(TOF) MS)-based metabolomics study to ide...
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doaj-2b9b77bf2f694592b03d31dba006dd6d2020-11-24T23:41:43ZengMDPI AGCancers2072-66942018-09-0110930010.3390/cancers10090300cancers10090300Targeted UPLC-MS Metabolic Analysis of Human Faeces Reveals Novel Low-Invasive Candidate Markers for Colorectal CancerJoaquin Cubiella0Marc Clos-Garcia1Cristina Alonso2Ibon Martinez-Arranz3Miriam Perez-Cormenzana4Ziortza Barrenetxea5Jesus Berganza6Isabel Rodríguez-Llopis7Mauro D’Amato8Luis Bujanda9Marta Diaz-Ondina10Juan M. Falcón-Pérez11Department of Gastroenterology, Complexo Hospitalario Universitario de Ourense, Instituto de Investigación Biomédica Ourense-Vigo-Pontevedra, 32005 Ourense, SpainExosomes Laboratory, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio, 48160 Bizkaia, SpainOWL Metabolomics, Bizkaia Technology Park, Derio, 48160 Bizkaia, SpainOWL Metabolomics, Bizkaia Technology Park, Derio, 48160 Bizkaia, SpainOWL Metabolomics, Bizkaia Technology Park, Derio, 48160 Bizkaia, SpainGAIKER-IK4 Technology Centre, Ed. 202, 48170 Zamudio, SpainGAIKER-IK4 Technology Centre, Ed. 202, 48170 Zamudio, SpainGAIKER-IK4 Technology Centre, Ed. 202, 48170 Zamudio, SpainGastrointestinal Genetics Unit, Biodonostia HRI, 20014 San Sebastián, SpainDepartment of Gastroenterology, Hospital Donostia/Instituto Biodonostia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universidad del País Vasco (UPV/EHU), 20014 San Sebastián, SpainDepartment of Gastroenterology, Complexo Hospitalario Universitario de Ourense, Instituto de Investigación Biomédica Ourense-Vigo-Pontevedra, 32005 Ourense, SpainExosomes Laboratory, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio, 48160 Bizkaia, SpainLow invasive tests with high sensitivity for colorectal cancer and advanced precancerous lesions will increase adherence rates, and improve clinical outcomes. We have performed an ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-(TOF) MS)-based metabolomics study to identify faecal biomarkers for the detection of patients with advanced neoplasia. A cohort of 80 patients with advanced neoplasia (40 advanced adenomas and 40 colorectal cancers) and 49 healthy subjects were analysed in the study. We evaluated the faecal levels of 105 metabolites including glycerolipids, glycerophospholipids, sterol lipids and sphingolipids. We found 18 metabolites that were significantly altered in patients with advanced neoplasia compared to controls. The combinations of seven metabolites including ChoE(18:1), ChoE(18:2), ChoE(20:4), PE(16:0/18:1), SM(d18:1/23:0), SM(42:3) and TG(54:1), discriminated advanced neoplasia patients from healthy controls. These seven metabolites were employed to construct a predictive model that provides an area under the curve (AUC) median value of 0.821. The inclusion of faecal haemoglobin concentration in the metabolomics signature improved the predictive model to an AUC of 0.885. In silico gene expression analysis of tumour tissue supports our results and puts the differentially expressed metabolites into biological context, showing that glycerolipids and sphingolipids metabolism and GPI-anchor biosynthesis pathways may play a role in tumour progression.http://www.mdpi.com/2072-6694/10/9/300colorectal cancermetabolomicsfaecal samplesbiomarkers |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Joaquin Cubiella Marc Clos-Garcia Cristina Alonso Ibon Martinez-Arranz Miriam Perez-Cormenzana Ziortza Barrenetxea Jesus Berganza Isabel Rodríguez-Llopis Mauro D’Amato Luis Bujanda Marta Diaz-Ondina Juan M. Falcón-Pérez |
spellingShingle |
Joaquin Cubiella Marc Clos-Garcia Cristina Alonso Ibon Martinez-Arranz Miriam Perez-Cormenzana Ziortza Barrenetxea Jesus Berganza Isabel Rodríguez-Llopis Mauro D’Amato Luis Bujanda Marta Diaz-Ondina Juan M. Falcón-Pérez Targeted UPLC-MS Metabolic Analysis of Human Faeces Reveals Novel Low-Invasive Candidate Markers for Colorectal Cancer Cancers colorectal cancer metabolomics faecal samples biomarkers |
author_facet |
Joaquin Cubiella Marc Clos-Garcia Cristina Alonso Ibon Martinez-Arranz Miriam Perez-Cormenzana Ziortza Barrenetxea Jesus Berganza Isabel Rodríguez-Llopis Mauro D’Amato Luis Bujanda Marta Diaz-Ondina Juan M. Falcón-Pérez |
author_sort |
Joaquin Cubiella |
title |
Targeted UPLC-MS Metabolic Analysis of Human Faeces Reveals Novel Low-Invasive Candidate Markers for Colorectal Cancer |
title_short |
Targeted UPLC-MS Metabolic Analysis of Human Faeces Reveals Novel Low-Invasive Candidate Markers for Colorectal Cancer |
title_full |
Targeted UPLC-MS Metabolic Analysis of Human Faeces Reveals Novel Low-Invasive Candidate Markers for Colorectal Cancer |
title_fullStr |
Targeted UPLC-MS Metabolic Analysis of Human Faeces Reveals Novel Low-Invasive Candidate Markers for Colorectal Cancer |
title_full_unstemmed |
Targeted UPLC-MS Metabolic Analysis of Human Faeces Reveals Novel Low-Invasive Candidate Markers for Colorectal Cancer |
title_sort |
targeted uplc-ms metabolic analysis of human faeces reveals novel low-invasive candidate markers for colorectal cancer |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2018-09-01 |
description |
Low invasive tests with high sensitivity for colorectal cancer and advanced precancerous lesions will increase adherence rates, and improve clinical outcomes. We have performed an ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-(TOF) MS)-based metabolomics study to identify faecal biomarkers for the detection of patients with advanced neoplasia. A cohort of 80 patients with advanced neoplasia (40 advanced adenomas and 40 colorectal cancers) and 49 healthy subjects were analysed in the study. We evaluated the faecal levels of 105 metabolites including glycerolipids, glycerophospholipids, sterol lipids and sphingolipids. We found 18 metabolites that were significantly altered in patients with advanced neoplasia compared to controls. The combinations of seven metabolites including ChoE(18:1), ChoE(18:2), ChoE(20:4), PE(16:0/18:1), SM(d18:1/23:0), SM(42:3) and TG(54:1), discriminated advanced neoplasia patients from healthy controls. These seven metabolites were employed to construct a predictive model that provides an area under the curve (AUC) median value of 0.821. The inclusion of faecal haemoglobin concentration in the metabolomics signature improved the predictive model to an AUC of 0.885. In silico gene expression analysis of tumour tissue supports our results and puts the differentially expressed metabolites into biological context, showing that glycerolipids and sphingolipids metabolism and GPI-anchor biosynthesis pathways may play a role in tumour progression. |
topic |
colorectal cancer metabolomics faecal samples biomarkers |
url |
http://www.mdpi.com/2072-6694/10/9/300 |
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