MFG-E8 promotes M2 polarization of macrophages and is associated with poor prognosis in patients with gastric cancer

Abstract

BackgroundMilk Fat Globule-Epidermal Growth Factor 8 (MFG-E8) has been reported to play an oncogenic role in a variety of tumors. However, its involvement in gastric cancer (GC) development has not been described. MethodsThe cancer genome atlas (TCGA) and the gene expression omnibus database (GEO) databases were used to analyze the expression of MFG-E8 in GC. These findings were further validated using immunohistochemistry (IHC) and western blotting assay (WB). Kaplan-Meier method, univariate logistic regression, and Christopher Cox regression were used to study the relationship between MFG-E8 and clinical pathology. In addition, the potential signaling pathways involved in MFG-E8 and its potential correlation with levels of immune cell infiltration were investigated. Finally, the biological function of MFG-E8 in GC cells was revealed. ResultsMFG-E8 was highly expressed in GC patients and cells, and the high level of MFG-E8 was associated with poor overall survival (OS). KEGG analysis indicated that MFG-E8 may play an important role in the cAMP signaling pathway. The expression of MFG-E8 was positively correlated with the infiltration of M2 macrophages. The patients with high MFG-E8 were easy to develop chemotherapy resistance. Furthermore, the knockdown of MFG-E8 significantly inhibited the proliferation and invasion of GC cells. ConclusionMFG-E8 in GC may serve as a prognostic marker and a potential immunotherapy target for GC.