Peptidomic and proteomic analysis of stool for diagnosing IBD and deciphering disease pathogenesis
In: Clinical Chemistry and Laboratory Medicine (CCLM), Jg. 58 (2020-03-26), S. 968-979
Online
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Zugriff:
Background The sensitivities and specificities of C-reactive protein (CRP) and faecal calprotectin (fCal), as recommended for inflammatory bowel diseases (IBD) diagnosis and monitoring, are low. Our aim was to discover new stool protein/peptide biomarkers for diagnosing IBD. Methods For peptides, MALDI-TOF/MS (m/z 1000–4000) was performed using stools from an exploratory (34 controls; 72 Crohn’s disease [CD], 56 ulcerative colitis [UC]) and a validation (28 controls, 27 CD, 15 UC) cohort. For proteins, LTQ-Orbitrap XL MS analysis (6 controls, 5 CD, 5 UC) was performed. Results MALDI-TOF/MS spectra of IBD patients had numerous features, unlike controls. Overall, 426 features (67 control-associated, 359 IBD-associated) were identified. Spectra were classified as control or IBD (absence or presence of IBD-associated features). In the exploratory cohort, the sensitivity and specificity of this classification algorithm were 81% and 97%, respectively. Blind analysis of the validation cohort confirmed 97% specificity, with a lower sensitivity (55%) paralleling active disease frequency. Following binary logistic regression analysis, IBD was independently correlated with MALDI-TOF/MS spectra (p m/z 1810.8 feature was a fragment of APC2, homologous with APC, over-expressed by infiltrating cells lining the surface in UC or the muscularis-mucosae in CD (assessed by immunohistochemistry). IBD-associated over-expressed proteins included immunoglobulins and neutrophil proteins, while those under-expressed comprised proteins of the nucleic acid assembly or those (OLFM4, ENPP7) related to cancer risk. Conclusions Our study provides evidence for the clinical utility of a novel proteomic method for diagnosing IBD and insight on the pathogenic role of APC. Moreover, the newly described IBD-associated proteins might become tools for cancer risk assessment in IBD patients.
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Peptidomic and proteomic analysis of stool for diagnosing IBD and deciphering disease pathogenesis
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Autor/in / Beteiligte Person: | Arrigoni, Giorgio ; Plebani, Mario ; Mescoli, Claudia ; D'Incà, Renata ; Padoan, Andrea ; Rugge, Massimo ; Contran, Nicole ; Bozzato, Dania ; Basso, Daniela ; Franchin, Cinzia ; Moz, Stefania ; Lorenzon, Greta ; Maria Luisa Scapellato |
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Zeitschrift: | Clinical Chemistry and Laboratory Medicine (CCLM), Jg. 58 (2020-03-26), S. 968-979 |
Veröffentlichung: | Walter de Gruyter GmbH, 2020 |
Medientyp: | unknown |
ISSN: | 1437-4331 (print) ; 1434-6621 (print) |
DOI: | 10.1515/cclm-2019-1125 |
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