Expression of 5-HT Relates to Stem Cell Marker LGR5 in Patients with Gastritis and Gastric Cancer

Abstract

Background5-Hydroxytryptamine (5-HT) and stem cells marker G-protein-coupled receptor 5 (LGR5) are associate with gastrointestinal inflammation and tumorigenesis. But the relationship between 5-HT and LGR5 is unclear.ObjectiveTo explore the expression and correlation of 5-HT and LGR5 in gastric mucosa of patients with gastritis and gastric cancer (GC).MethodsA total of 41 patients with GC and 98 patients with chronic gastritis were included in this study. The expression of TPH1 mRNA, LGR5 mRNA and β-catenin mRNA in gastric mucosa were explored by Real-time Quantitative polymerase chain reaction (qPCR). 5-HT-positive cells and LGR5-positive cells in gastric mucosa were detected by immunohistochemistry stains. The co-localization of 5-HT and chromogranin A (CgA), 5-HT receptor4 (5-HTR4) and LGR5 were detected by multiplex immunofluorescence.ResultsThe expression of 5-HT and LGR5 in patients with GC was significantly higher than patients with chronic gastritis (p < 0.05). The positive rate of 5-HT and LGR5 increased sequentially in the patients with non-atrophic gastritis, intestinal metaplasia and GC, which were 18.52%, 35.56% and 75.61% for 5-HT, and 27.78%, 40.91% and 95.12% for LGR5, respectively. The expression of 5-HT and LGR5 was positively correlated in gastritis and GC patients (p < 0.05). Moreover, the expression level of TPH1 mRNA and LGR5 mRNA was also positively correlated in gastritis patients (r = 0.7377, p < 0.001). Besides, 5-HT was partially co-localized with CgA, and 5-HTR4 was co-localized with LGR5 in gastric mucosa.ConclusionThe increase of 5-HT synthesis in gastric mucosa may have an impact on LGR5-positive gastric epithelial stem cells.