Expression of 5-HT Relates to Stem Cell Marker LGR5 in Patients with Gastritis and Gastric Cancer
Qian Niu, Lin Li, Caili Zhang, Changhai Qi, Qiufeng He, Yuanmin Zhu
Abstract
BACKGROUND: 5-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. OBJECTIVE: To explore the expression and correlation of 5-HT and LGR5 in gastric mucosa of patients with gastritis and gastric cancer (GC). METHODS: A 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. RESULTS: The 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. CONCLUSION: The increase of 5-HT synthesis in gastric mucosa may have an impact on LGR5-positive gastric epithelial stem cells.