title: Biomarkers of human gastrointestinal tract regions.
abstract: Dysregulation of intestinal epithelial cell performance is associated with an array of pathologies whose onset mechanisms are incompletely understood. While whole-genomics approaches have been valuable for studying the molecular basis of several intestinal diseases, a thorough analysis of gene expression along the healthy gastrointestinal tract is still lacking. The aim of this study was to map gene expression in gastrointestinal regions of healthy human adults and to implement a procedure for microarray data analysis that would allow its use as a reference when screening for pathological deviations. We analyzed the gene expression signature of antrum, duodenum, jejunum, ileum, and transverse colon biopsies using a biostatistical method based on a multivariate and univariate approach to identify region-selective genes. One hundred sixty-six genes were found responsible for distinguishing the five regions considered. Nineteen had never been described in the GI tract, including a semaphorin probably implicated in pathogen invasion and six novel genes. Moreover, by crossing these genes with those retrieved from an existing data set of gene expression in the intestine of ulcerative colitis and Crohn's disease patients, we identified genes that might be biomarkers of Crohn's and/or ulcerative colitis in ileum and/or colon. These include CLCA4 and SLC26A2, both implicated in ion transport. This study furnishes the first map of gene expression along the healthy human gastrointestinal tract. Furthermore, the approach implemented here, and validated by retrieving known gene profiles, allowed the identification of promising new leads in both healthy and disease states.
authors.affiliation: Department of Nutrition and Health, Nestlé Research Center, Vers chez les Blanc, Lausanne, Switzerland. elena.comelli@utoronto.ca
authors.forename: Elena Maria
authors.initials: EM
authors.lastname: Comelli
authors.forename: Sofiane
authors.initials: S
authors.lastname: Lariani
authors.forename: Marie-Camille
authors.initials: MC
authors.lastname: Zwahlen
authors.forename: Grigorios
authors.initials: G
authors.lastname: Fotopoulos
authors.forename: James Anthony
authors.initials: JA
authors.lastname: Holzwarth
authors.forename: Christine
authors.initials: C
authors.lastname: Cherbut
authors.forename: Gian
authors.initials: G
authors.lastname: Dorta
authors.forename: Irène
authors.initials: I
authors.lastname: Corthésy-Theulaz
authors.forename: Martin
authors.initials: M
authors.lastname: Grigorov
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D005260:Female; D005767:Gastrointestinal Diseases / Q000235:genetics* / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000378:metabolism*; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D055815:Young Adult
chemical_list: D015415:Biomarkers