التفاصيل البيبلوغرافية
| العنوان: |
Peptidomic and proteomic analysis of stool for diagnosing IBD and deciphering disease pathogenesis. |
| المؤلفون: |
Basso, Daniela, Padoan, Andrea, D'Incà, Renata, Arrigoni, Giorgio, Scapellato, Maria Luisa, Contran, Nicole, Franchin, Cinzia, Lorenzon, Greta, Mescoli, Claudia, Moz, Stefania, Bozzato, Dania, Rugge, Massimo, Plebani, Mario |
| المصدر: |
Clinical Chemistry & Laboratory Medicine; Jun2020, Vol. 58 Issue 6, p968-979, 12p, 1 Color Photograph, 4 Charts, 2 Graphs |
| مصطلحات موضوعية: |
INFLAMMATORY bowel diseases, CROHN'S disease, ULCERATIVE colitis, LOGISTIC regression analysis, CALPROTECTIN, C-reactive protein |
| مستخلص: |
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 < 0.0001), outperforming fCal measurements (p = 0.029). The IBD-correlated 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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
