ArticleThe Annals of otology, rhinology, and laryngology2015
Local Synthesis of Pepsin in Barrett's Esophagus and the Role of Pepsin in Esophageal Adenocarcinoma.
Article in The Annals of otology, rhinology, and laryngology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- Amprenavir Mitigates Pepsin-Induced Transcriptomic Changes in Normal and Precancerous Esophageal Cells.International journal of molecular sciences · 2025Article
- Identification ofDiagnostics (Basel, Switzerland) · 2024Article
- Global Transcriptomic Analysis of Topical Sodium Alginate Protection against Peptic Damage in an In Vitro Model of Treatment-Resistant Gastroesophageal Reflux Disease.International journal of molecular sciences · 2024Article
- Topical Alginate Protection against Pepsin-Mediated Esophageal Damage: E-Cadherin Proteolysis and Matrix Metalloproteinase Induction.International journal of molecular sciences · 2023Article
- The Protease Inhibitor Amprenavir Protects against Pepsin-Induced Esophageal Epithelial Barrier Disruption and Cancer-Associated Changes.International journal of molecular sciences · 2023Article
- Cancer Risk in Barrett's Esophagus: A Clinical Review.International journal of molecular sciences · 2023Review
- Trends in gastroesophageal reflux disease research: A bibliometric and visualized study.Frontiers in medicine · 2022Article
- Pepsin and Laryngeal and Hypopharyngeal Carcinomas.Clinical and experimental otorhinolaryngology · 2021Review
- Multivariate gene expression-based survival predictor model in esophageal adenocarcinoma.Thoracic cancer · 2020Article
- Pepsin promotes IL-8 signaling-induced epithelial-mesenchymal transition in laryngeal carcinoma.Cancer cell international · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveDespite widespread use of proton pump inhibitors (PPIs), the incidence of esophageal adenocarcinoma (EAC) continues to rise. PPIs reduce reflux acidity, but only transiently inactivate gastric enzymes. Nonacid reflux, specifically nonacid pepsin, contributes to carcinogenesis in the larynx. Given the carcinogenic potential of pepsin and inefficacy of PPIs to prevent EAC, the presence and effect of pepsin in the esophagus should be investigated.
methodsNormal and Barrett's biopsies from 8 Barrett's esophagus patients were collected for pepsin analysis via Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). Human esophageal cells cultured from healthy patients were treated with pepsin (0.01-1 mg/mL; 1-20 hours), acid (pH 4)±pepsin (5 minutes); real-time RT-PCR, ELISA, and cell migration were assayed.
resultsPepsin was detected in all 8 Barrett's and 4 of 8 adjacent normal specimens. Pepsinogen mRNA was observed in 22 Barrett's, but not in normal adjacent samples. Pepsin induced PTSG2 (COX-2) and IL-1β expression and cell migration in vitro.
conclusionsPepsin is synthesized by metaplastic, Barrett's esophageal mucosa. Nonacid pepsin increases metrics of tumorigenicity in esophageal epithelial cells in vitro. These findings implicate refluxed and locally synthesized pepsin in development and progression of EAC and, in part, explain the inefficacy of PPIs in the prevention of EAC.
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