Immunohistochemical Analysis of Lgr5 and Troy Expression in Gastric Carcinogenesis Demonstrates an Inverse Trend Publisher Pubmed



Saberi S¹ ; Piryaei A^{2, 3} ; Mirabzadeh E⁴ ; Esmaeili M¹ ; Karimi T¹ ; Momtaz S¹ ; Abdirad A⁵ ; Sodeifi N⁶ ; Mohagheghi MA⁷ ; Baharvand H³ ; Mohammadi M¹ Show Affiliations
Source: Iranian Biomedical Journal Published:2019

Abstract

Background: Two of the Wnt signaling pathway target genes, tumor necrosis factor receptor family member (TROY) and leucine-rich G-protein coupled receptor (LGR5), are involved in the generation and maintenance of gastrointestinal epithelium. A negative modulatory role has recently been assigned to TROY, in this pathway. Here, we have examined their simultaneous expression in gastric carcinogenesis. Methods: Tumor and paired adjacent tissues of intestinal-type gastric cancer (GC) patients (n = 30) were evaluated for LGR5 and TROY expression by immunohistochemistry. The combination of the percentage of positively stained cells and the intensity of staining was defined as the composite score and compared between groups. The obtained findings were re-evaluated in a mouse model. Results: TROY expression in the tumor tissue was significantly lower than that of the adjacent tissue (2.5 ± 0.9 vs. 3.3 ± 0.9, p = 0.004), which was coincident with higher LGR5 expression (3.6 ± 1.1 vs. 2.7 ± 0.9, p = 0.001). This observation was prominent at stages II/III of GC, leading to a statistically significant mean difference of expression between these two molecules (p = 0.005). In the H. pylori infected-mouse model, this inverse expression was observed in transition from early (8-16 w) to late (26-50 w) time points, post treatment (p = 0.002). Conclusion: Our data demonstrates an inverse trend between TROY down-regulation and LGR5 up-regulation in GC tumors, as well as in response to H. pylori infection in mice. These findings support a potential negative modulatory role for TROY on LGR5 expression. expression. © 2019, Pasteur Institute of Iran. All rights reserved.