Concordance between gene expression in peripheral whole blood and colonic tissue in children with inflammatory bowel disease


Autoři: Nathan P. Palmer aff001;  Jocelyn A. Silvester aff002;  Jessica J. Lee aff002;  Andrew L. Beam aff001;  Inbar Fried aff001;  Vladimir I. Valtchinov aff001;  Fedik Rahimov aff004;  Sek Won Kong aff005;  Saum Ghodoussipour aff002;  Helen C. Hood aff002;  Athos Bousvaros aff002;  Richard J. Grand aff002;  Louis M. Kunkel aff004;  Isaac S. Kohane aff001
Působiště autorů: Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, United States of America aff001;  Division of Gastroenterology and Nutrition, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America aff002;  Center for Evidence Based Imaging, Brigham and Women’s Hospital, Harvard Medical School, Massachusetts, United States of America aff003;  Division of Genetics and Genomics, Boston Children’s Hospital, Departments of Genetics and Pediatrics, Harvard Medical School, Boston, Massachusetts, United States of America aff004;  Computational Health Informatics Program, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America aff005
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222952

Souhrn

Background

Presenting features of inflammatory bowel disease (IBD) are non-specific. We hypothesized that mRNA profiles could (1) identify genes and pathways involved in disease pathogenesis; (2) identify a molecular signature that differentiates IBD from other conditions; (3) provide insight into systemic and colon-specific dysregulation through study of the concordance of the gene expression.

Methods

Children (8–18 years) were prospectively recruited at the time of diagnostic colonoscopy for possible IBD. We used transcriptome-wide mRNA profiling to study gene expression in colon biopsies and paired whole blood samples. Using blood mRNA measurements, we fit a regression model for disease state prediction that was validated in an independent test set of adult subjects (GSE3365).

Results

Ninety-eight children were recruited [39 Crohn’s disease, 18 ulcerative colitis, 2 IBDU, 39 non-IBD]. There were 1,118 significantly differentially (IBD vs non-IBD) expressed genes in colon tissue, and 880 in blood. The direction of relative change in expression was concordant for 106/112 genes differentially expressed in both tissue types. The regression model from the blood mRNA measurements distinguished IBD vs non-IBD disease status in the independent test set with 80% accuracy using only 6 genes. The overlap of 5 immune and metabolic pathways in the two tissue types was significant (p<0.001).

Conclusions

Blood and colon tissue from patients with IBD share a common transcriptional profile dominated by immune and metabolic pathways. Our results suggest that peripheral blood expression levels of as few as 6 genes (IL7R, UBB, TXNIP, S100A8, ALAS2, and SLC2A3) may distinguish patients with IBD from non-IBD.

Klíčová slova:

Biopsy – Blood – Colon – Crohn's disease – Endoscopy – Gene expression – Inflammatory bowel disease – Ulcerative colitis


Zdroje

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