Involvement of CXCL17 and GPR35 in Gastric Cancer Initiation and Progression

The expression of CXC motif chemokine 17 (CXCL17) and its reported membrane receptor G-protein-coupled receptor 35 (GPR35) in different gastric pathological lesions and their clinical implications are largely unknown. In this study, a total of 860 pathological sections were immune-stained with either anti-CXCL17 or anti-GPR35 antibodies. Their expression was scored within the area of the normal gastric gland of non-atrophic gastritis (NAG-NOR), intestinal metaplasia of atrophic gastritis (AG-IM), IM adjacent to GC (GC-IM), and GC tissue. The clinical significance and potential function of CXCL17 and GPR35 were explored using multiple methods. Our results suggested that CXCL17 expression was gradually upregulated during the pathological progress of gastric diseases (NAG-NOR < AG-IM < GC-IM), but significantly downregulated when GC occurred. GPR35 had a similar expression pattern but its expression in GC remained abundant. High CXCL17 expression in GC was associated with less malignant behavior and was an independent biomarker of favorable prognosis. Overexpressing CXCL17 in HGC27 cells significantly upregulated CCL20 expression. TCGA analysis identified that CXCL17 was negatively correlated with some cancer-promoting pathways and involved in inflammatory activities. CTRP analysis revealed that gastric cell lines expressing less CXCL17 and were more sensitive to the CXCR2 inhibitor SB-225002.

Automated summary

The expression of CXCL17 and its receptor GPR35 in different gastric pathological lesions was investigated in this study. The results showed that CXCL17 expression gradually increased during the progression of gastric diseases, but significantly decreased in gastric cancer. GPR35 had a similar expression pattern but remained abundant in gastric cancer. High CXCL17 expression in gastric cancer was associated with less malignant behavior and favorable prognosis. Overexpressing CXCL17 in HGC27 cells upregulated CCL20 expression. In addition, CXCL17 was involved in cancer-promoting pathways and inflammatory activities.