Study On The Correlation And Mechanism Of PLXDC2 With Prognosis And Immune Infiltration Of Gastric Cancer

Background:PLXDC2(Plexin domain containing 2)is a transmembrane protein that can promote tumor blood vessel formation and participate in the regulation of macrophages.It has been studied in breast cancer,colon cancer,ovarian cancer,liver cancer and other cancers.However,the effect of PLXDC2 on the prognosis and immune infiltration of gastric cancer remains to be unclear.Objective:To analyze the expression level and prognostic value of PLXDC2 in gastric cancer,and explore its correlation with immune infiltration;further explore the potential molecular mechanism of PLXDC2 in gastric cancer.Method:We used Oncomine,GEPIA,Kaplan-Meier plotter and UALCAN database to analyze the expression level of PLXDC2 in gastric cancer tissues and its relationship with the overall survival(OS)of gastric cancer patients,and evaluated the relationship between PLXDC2 and gastric cancer immune invasion from the TIMER and GEPIA databases,and the correlation between PLXDC2 and YAP1 expression was also analyzed in the GEPIA database;immunohistochemistry and western blotting were used to detect the expression level of PLXDC2 in gastric cancer cells and tissues,and the clinical pathological information and follow-up data were used to explore the correlation between the expression level of PLXDC2 and the clinicopathological characteristics and prognosis of gastric cancer,after regulating the expression of PLXDC2 in gastric cancer cell lines,we observe the changes of YAP1 and PD-L1 expression and explore the molecular mechanism of PLXDC2 in gastric cancer.Result:Bioinformatics online database analysis results suggest that the expression of PLXDC2 in gastric cancer is higher than that in adjacent normal tissues,and the high expression is associated with worse overall survival of patients.In addition,the expression of PLXDC2 is positively correlated with the infiltration level of CD4 + T cells,CD8 + T cells,macrophages,neutrophils and dendritic cells in the microenvironment of gastric cancer,and closely correlated with gene markers of various immune cell.In addition,the expression of PLXDC2 is significantly correlated with the expression of YAP1.Immunohistochemistry showed that PLXDC2 is highly expressed in gastric cancer tissues and is positively correlated with YAP1 expression,PD-L1 expression,and CD8+ T cell infiltration;clinicopathological information and follow-up data analysis suggest that PLXDC2 expression is related to tissue differention,depth of invasion,lymph node metastasis,clinical stage,and has no significant correlation with other clinicopathological characteristics.Kaplan-Meier survival analysis suggests that patients with gastric cancer with high PLXDC2 expression have shorter overall survival.Univariate and multivariate survival analyses indicate that high PLXDC2 expression is an independent adverse factor affecting the overall survival of patients with gastric cancer.Western blot experiments showed that the expression of PLXDC2 in gastric cancer cell lines was higher than that in normal gastric mucosal epithelial cell lines;after the expression of PLXDC2 was down-regulated,the protein levels of YAP1 and PD-L1 were also decreased.Conclusion:This study confirmed that the expression of PLXDC2 is elevated in gastric cancer tissues and cells,and it suggests a poor prognosis.The expression level of PLXDC2 affects the immune infiltration of gastric cancer tumor microenvironment.PLXDC2 can regulate the expression of PD-L1 through YAP1,which may affect the efficacy of tumor immunotherapy.Therefore,we conclude that PLXDC2 can act as an independent predictive marker for the prognosis of gastric cancer,and might be useful as a potential reference value for the relief and immunotherapy of gastric cancer.