TY - JOUR
T1 - Targeted UPLC-MS metabolic analysis of human faeces reveals novel low-invasive candidate markers for colorectal cancer
AU - Cubiella, Joaquin
AU - Clos-Garcia, Marc
AU - Alonso, Cristina
AU - Martinez-Arranz, Ibon
AU - Perez-Cormenzana, Miriam
AU - Barrenetxea, Ziortza
AU - Berganza, Jesus
AU - Rodríguez-Llopis, Isabel
AU - D’amato, Mauro
AU - Bujanda, Luis
AU - Diaz-Ondina, Marta
AU - Falcón-Pérez, Juan M.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - 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.
AB - 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.
KW - Biomarkers
KW - Colorectal cancer
KW - Faecal samples
KW - Metabolomics
UR - http://www.scopus.com/inward/record.url?scp=85053007307&partnerID=8YFLogxK
U2 - 10.3390/cancers10090300
DO - 10.3390/cancers10090300
M3 - Article
AN - SCOPUS:85053007307
SN - 2072-6694
VL - 10
JO - Cancers
JF - Cancers
IS - 9
M1 - 300
ER -
