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. 2017 Sep;66(9):1573-1583.
doi: 10.1136/gutjnl-2015-310705. Epub 2016 May 23.

Proteomic analysis of ascending colon biopsies from a paediatric inflammatory bowel disease inception cohort identifies protein biomarkers that differentiate Crohn's disease from UC

Amanda E Starr  1 , Shelley A Deeke  1 , Zhibin Ning  1 , Cheng-Kang Chiang  1 , Xu Zhang  1 , Walid Mottawea  1   2 , Ruth Singleton  3 , Eric I Benchimol  3   4   5 , Ming Wen  1 , David R Mack  3   4 , Alain Stintzi  1 , Daniel Figeys  1   6
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"V体育安卓版" Proteomic analysis of ascending colon biopsies from a paediatric inflammatory bowel disease inception cohort identifies protein biomarkers that differentiate Crohn's disease from UC

Amanda E Starr et al. Gut. 2017 Sep.

Abstract

Objective: Accurate differentiation between Crohn's disease (CD) and UC is important to ensure early and appropriate therapeutic intervention. We sought to identify proteins that enable differentiation between CD and UC in children with new onset IBD VSports手机版. .

Design: Mucosal biopsies were obtained from children undergoing baseline diagnostic endoscopy prior to therapeutic interventions. Using a super-stable isotope labeling with amino acids in cell culture (SILAC)-based approach, the proteomes of 99 paediatric control and biopsies of patients with CD and UC were compared. Multivariate analysis of a subset of these (n=50) was applied to identify novel biomarkers, which were validated in a second subset (n=49) V体育安卓版. .

Results: In the discovery cohort, a panel of five proteins was sufficient to distinguish control from IBD-affected tissue biopsies with an AUC of 1. 0 (95% CI 0. 99 to 1. 0); a second panel of 12 proteins segregated inflamed CD from UC within an AUC of 0. 95 (95% CI 0. 86 to 1. 0). Application of the two panels to the validation cohort resulted in accurate classification of 95. 9% (IBD from control) and 80% (CD from UC) of patients. 116 proteins were identified to have correlation with the severity of disease, four of which were components of the two panels, including visfatin and metallothionein-2 V体育ios版. .

Conclusions: This study has identified two panels of candidate biomarkers for the diagnosis of IBD and the differentiation of IBD subtypes to guide appropriate therapeutic interventions in paediatric patients. VSports最新版本.

Keywords: CROHN'S DISEASE; IBD; IBD BASIC RESEARCH; ULCERATIVE COLITIS. V体育平台登录.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
(A) Principal component analysis (PCA) of the Q95+subgroup-specific proteins showing separation of IBD inflamed ascending colon patients proteomes (UC, red; Crohn's disease (CD), blue) from controls (black) and from non-inflamed CD ascending colon (CoN) (grey) based on the of Q95+subgroup-specific proteins.
Figure 2
Figure 2
Partial Least Squares Discriminant Analyses (PLSDA) models were trained using data from the discovery cohort and then tested with the data from the validation cohort. They were used to classify control and patients with IBD (inflamed ascending colon biopsy). (A) Relative expression levels of the five candidate biomarkers (panel 1) to separate control from patients with IBD. (B) Panel 1 receiving operating characteristics (ROC) curve of the discovery cohort (blue) and validation cohort (pink) and (C) associated prediction overview for classification using the panel 1 PLSDA model wherein patients to the left of 0.5 would classify as controls and to the right of 0.5 would classify as IBD; true diagnoses of individual patient samples from the discovery and validation cohorts are shown in open or closed symbols, respectively. (D) Principal component analysis using five biomarkers to distinguish IBD (purple) from control (black) population in the discovery and validation cohorts. Statistical significance by Student's t test with ****p<0.0001.
Figure 3
Figure 3
Partial Least Squares Discriminant Analyses (PLSDA) models were trained using data from the discovery cohort and then tested with the data from the validation cohort to classify patients with Crohn's disease (CD) and UC from inflamed ascending colon biopsies. (A) Relative expression levels of the 12 candidate biomarkers (panel 2) to separate patients with CD from those with UC. (B) Panel 2 receiving operating characteristics (ROC) curve of the discovery cohort (blue) and validation cohort (pink) and (C) associated prediction overview for classification using the panel 2 PLSDA model wherein patients to the left of 0.5 would classify as CD and to the right of 0.5 would classify as UC; true diagnoses of individual patient samples from the discovery and validation cohorts are shown in open or closed symbols, respectively. (D) Principal component analysis using 12 biomarkers to distinguish CD (blue) from UC (red) population in the discovery and validation cohorts. Statistical significance by Student's t test with *p<0.05, **p<0.005.
Figure 4
Figure 4
(A) Biological processes of 106 candidate biomarker proteins that contribute to segregation of IBD from control. (B) Metabolic pathways that differ within IBD subtypes; proteins that are upregulated in Crohn's disease (blue lines) are associated with fatty acid metabolism and oxidative phosphorylation, whereas amino acid and energy metabolism are elevated in UC candidate biomarkers (red lines). Pathways with some overlap are shown (dark purple lines). Amino acid metabolism shown with single letter code for alanine (A), aspartic acid (D), glutamic acid (E), arginine (R), proline (P), cysteine (C) and methionine (M).
Figure 5
Figure 5
(A) Venn diagram of the number of proteins that correlated with severity of disease in patients with Crohn's disease (CD) (blue) or UC (red) as determined by Pearson correlation analysis of the Pediatric Crohn's Disease Activity Index (PCDAI) or Pediatric UC Activity Index (PUCAI) score with the Q95 proteins+subgroup-specific proteins. (B–E) Scatter plots of the relative expression of proteins with significant correlation to severity score that are part of the (B and C) IBD versus control panel, and (D and E) CD versus UC panel are shown.
Figure 6
Figure 6
(A) Amount of visfatin per milligram of biopsy protein, determined by enzyme-linked immunosorbent assay (ELISA) in a subset of the validation cohort. (B) Amount of metallothionein-2 (MT2) per milligram of biopsy total protein determined by ELISA in a subset of the validation cohort. (C) Correlation between the ELISA-measured amount of MT2 and the corresponding patient Pediatric Crohn's Disease Activity Index (PCDAI) score in a subset of the Crohn's disease (CD) validation cohort. n=8 each for control, patients with CD and patients with UC.
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References (V体育2025版)

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