ADAM12 Facilitates Tumor Progression By Enhancing Metastasis And Immune Infiltration In Gastric Cancer

Objective: A disintergin and metalloprotease（ADAM）12,an essential transmembrane protein with extracellular metalloprotease activity,cell binding and intracellular signaling properties,was reported to play a crucial role in cancers.However,the biological function of ADAM12 in gastric cancer（GC）remains unclear.In this study,the expression level,prognostic value,regulation mechanism and biological function of ADAM12 in GC were comprehensively explored by bioinformatics and experiments analyses,so as to highlight the potential of ADAM12 as a prognostic biomarker and therapy target in GC.Methods:Gene expression Profiling Interactive Analysis（GEPIA）and the GSE19826 dataset obtained from the GEO database were used to determine the expression level of ADAM12 in GC,and the prognostic value of ADAM12 in GC was also confirmed by GEPIA database.Moreover,the expression level and prognostic value of ADAM12 in GC were verified by experimental and clinicopathological data analysis.The level of DNA methylation and the ce RNA network were identified using the Meth Surv,Starbase3.0 and mi RNet2.0 databases.Then,the co-expression profiles of ADAM12 were determined and subjected to perform enrichment analysis using the Linked Omics database.The protein-protein interaction network and the docking model of ADAM12 were constructed using the Gene MANIA,STRING,and HDOCK webservers.The role of ADAM12 in tumor metastasis and immune infiltration was explored using in vitro assays and TIMER database analysis.Results: Bioinformatics analysis found that ADAM12 was overexpressed and correlated with a poor prognosis of GC patients.The results of experimental and clinicopathological data analysis also verified this result.And the aberrant DNA methylation status and ce RNA regulation may contribute to the upregulation of ADAM12 in GC.Co-expression gene profiles analysis by Linked Omics found that a total of 9,307 genes were found to be significantly positively correlated with ADAM12,while 10,919 genes showed significantly negative correlations.Moreover,the enrichment analysis revealed that ADAM12 is involved in multiple vital biological functions and pathways,such as “macrophage activation”,“extracellular matrix binding”and “ECM-receptor interaction”.Subsequently,the protein-protein interaction network and molecular docking model demonstrated that FSTL3 is a potential binding partner of ADAM12.The in vitro assay demonstrated that ADAM12 overexpression significantly promotes the migration and invasion abilities of AGS cells,while ADAM12 knockdown significantly reduces the migration and invasion ability of HGC27 cells.Finally,bioinformatics demonstrated that ADAM12 promotes immune infiltration and M2 macrophage polarization in GC.Conclusion: In summary,elevation of ADAM12 facilitates tumor progression by enhancing metastasis and immune infiltration in gastric cancer,and these results highlighted the potential of ADAM12 to be used as a therapy target in GC.