title: Metabolomic Analysis of Gastric Cancer Progression within the Correa's Cascade Using Ultraperformance Liquid Chromatography-Mass Spectrometry.
abstract: Gastric cancer (GC) is among the most common cancers worldwide. Gastric carcinogenesis is a multistep and multifactorial process beginning with chronic gastritis induced by Helicobacter pylori (H. pylori) infection. This process is often described via a sequence of events known as Correas's cascade, a stepwise progression from nonactive gastritis, chronic active gastritis, precursor lesions of gastric cancer (atrophy, intestinal metaplasia, and dysplasia), and finally adenocarcinoma. Our aim was to identify a plasma metabolic pattern characteristic of GC through disease progression within the Correa's cascade. This study involved the analysis of plasma samples collected from 143 patients classified in four groups: patients with nonactive gastritis and no H. pylori infection, H. pylori infected patients with chronic active gastritis, infected or noninfected patients with precursor lesions of gastric cancer, and GC. Independent partial least-squares-discriminant binary models of UPLC-ESI(+)-TOFMS metabolic profiles, implemented in a decision-directed acyclic graph, allowed the identification of tryptophan and kynurenine as discriminant metabolites that could be attributed to indoleamine-2,3-dioxygenase upregulation in cancer patients leading to tryptophan depletion and kynurenine metabolites generation. Furthermore, phenylacetylglutamine was also classified as a discriminant metabolite. Our data suggest the use of tryptophan, kynurenine, and phenylacetylglutamine as potential GC biomarkers.
authors.forename: Julia
authors.initials: J
authors.lastname: Kuligowski
authors.affiliation: Safety and Sustainability Division, Leitat Technological Center , Barcelona 08028, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sanjuan-Herráez
authors.affiliation: Safety and Sustainability Division, Leitat Technological Center , Barcelona 08028, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Vázquez-Sánchez
authors.forename: Anna
authors.initials: A
authors.lastname: Brunet-Vega
authors.forename: Carles
authors.initials: C
authors.lastname: Pericay
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III , Madrid 28029, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Ramírez-Lázaro
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III , Madrid 28029, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Lario
authors.affiliation: Safety and Sustainability Division, Leitat Technological Center , Barcelona 08028, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Gombau
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III , Madrid 28029, Spain.
authors.forename: Félix
authors.initials: F
authors.lastname: Junquera
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III , Madrid 28029, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Calvet
authors.affiliation: Safety and Sustainability Division, Leitat Technological Center , Barcelona 08028, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Quintás
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D018450:Disease Progression; D005260:Female; D005756:Gastritis / Q000378:metabolism; D005973:Glutamine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D016481:Helicobacter Infections; D016480:Helicobacter pylori; D006801:Humans; D007737:Kynurenine / Q000032:analysis / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D010949:Plasma / Q000378:metabolism; D011230:Precancerous Conditions / Q000378:metabolism; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D014364:Tryptophan / Q000032:analysis / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D005973:Glutamine; D007737:Kynurenine; D014364:Tryptophan; C003089:phenylacetylglutamine
keywords: Helicobacter pylori; UPLC-MS; gastric cancer; indoleamine-2,3-dioxygenase; metabolomics; phenylacetylglutamine; tryptophan