Distinct proteomic profiles characterise non‐erosive from erosive reflux disease

• Published in: Alimentary pharmacology & therapeutics 2011-10, Vol.34 (8), p.982-993
• Main Authors: Calabrese, C., Marzano, V., Urbani, A., Lazzarini, G., Valerii, M. C., Liguori, G., Di Molfetta, S., Rizzello, F., Gionchetti, P., Campieri, M., Spisni, E.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Biomarkers - metabolism; Biopsy; Blotting, Western; Case-Control Studies; Digestive system; Endoscopy, Gastrointestinal; Esophageal pH Monitoring; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gastroesophageal Reflux - metabolism; Gene Expression Profiling - methods; Humans; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Proteome - metabolism; Proteomics - methods; Severity of Illness Index; Young Adult
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/j.1365-2036.2011.04801.x

Aliment Pharmacol Ther 2011; 34: 982–993 Summary Background  Erosive reflux disease (ERD) and non‐erosive reflux disease (NERD) are often regarded as part of the spectrum of the same disease. Aim  To elucidate molecular features that characterise NERD and ERD at the protein level. Methods  A total of 56 consecutive subjects were enrolled: 10 healthy subjects, 24 with NERD and 22 with ERD. Eight specimens were taken from macroscopically normal mucosa at 5 cm of gastro‐oesophageal junction. Four were processed for the proteins extraction and four for evaluation using haematoxylin‐eosin and immunohistochemistry. We used shotgun proteomics to identify tentative disease molecular features for ERD or NERD. Candidate distinctive proteins were verified using immunohistochemistry. Results  Shotgun proteomics analysis revealed 33 differentially expressed proteins in NERD vs. ERD samples, involved in cellular proliferation, keratinisation, stress responses and sugar metabolism. Based on a gene ontology meta‐analysis, seven of them were further analysed using Western blotting (WB) and four also using immunohistochemistry. We identified novel candidate disease molecular features for GERD and few distinctive proteins to discriminate NERD and ERD. In particular, Transitional Endoplasmic Reticulum ATPase (TER ATPase), GAPDH, Alpha 1 Acid Glycoprotein 1, Annexin A1, Calmodulin and 14‐3‐3 proteins were confirmed at WB analysis. Conclusions  Non‐erosive reflux disease and ERD are distinct disease entities at the protein level. This study proposes an array of candidate biomarkers possibly useful to discriminate between NERD and ERD.