Identification of serum proteome signature of irritable bowel syndrome: Potential utility of the tool for early diagnosis and patient's stratification

Abstract

Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder with high incidence, and great heterogeneity of symptoms. Numerous factors are correlated with IBS development; however, the pathophysiology is not yet clear. In addition, there is no appropriate diagnostic tool available. The aim of this study was the identification of protein expression alterations in IBS patients compared to healthy individuals. Serum samples from 30 IBS patients (10 with IBS-Diarrhea, 10 IBS-Constipation and 10 IBS-Mixed) and 10 healthy individuals were subjected to proteomic analysis by 2-dimensional gel electrophoresis. Following evaluation of densitometrical data, protein spots exhibiting differential expression among the groups, were further characterized by matrix-assisted laser desorption tandem time-of-flight mass spectrometer and the results were confirmed by Western blot analysis. Eight significantly different expressed proteins were identified. Seven of them were overexpressed in IBS cases and only one was overexpressed in healthy individuals. These proteins were also differently expressed between the three IBS subgroups. IBS-D group overexpressed immunoglobulin light chain Lambda (LAC3) and apolipoprotein E (APOE), IBS-C group overexpressed apolipoprotein H (APOH) and collagen alpha-1 (XIV) chain (COEA1), and IBS-M group and healthy individuals overexpressed retinol-binding protein 4 (RET4). Our results show a different serum protein profile of IBS patients compared to healthy controls. Understanding the role of these eight proteins which are differently expressed in IBS patients, may contribute to a better clarification of IBS pathogenesis and to patient's stratification.

Significance: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder with high incidence and great heterogeneity of symptoms without any appropriate diagnostic tool available. Eight significantly different expressed proteins were identified. Seven of them were overexpressed in IBS cases and only one was expressed in healthy individuals. These proteins were also differently expressed between the three IBS subgroups. Our results show that there is a different serum proteome signature in IBS compared to healthy individuals, as well as in IBS subgroups that could be used in the future for patient's stratification and as a diagnostic tool.

Keywords: Biomarkers; IBS-Constipation; IBS-Diarrhea; IBS-Mixed; Irritable bowel syndrome; Patient stratification; Proteomics.