Unveiling the significance of ADAM12 through pan-cancer analysis and experimental verification in gastric cancer.

BACKGROUND: ADAM12, a member of the disintegrin and metalloproteinase family, has been involved in multiple cancers, yet its precise role in pan-cancer progression still remains elusive. METHODS: In our current study, we conducted a comprehensive analysis of ADAM12 expression, diagnosis, prognosis, genomic variations, DNA methylation, functional enrichment, immune infiltration as well as immunotherapy in pan-cancer utilizing public datasets. Additionally, a series of biological functional experiments of ADAM12 were performed in gastric cancer cells including cell counting kit-8 (CCK-8), colony formation, wound healing analysis, and Transwell analyses. RESULTS: ADAM12 expression was prominently elevated and correlated with unfavorable prognosis in most cancer types. It exhibited elevated mutation frequency and a negative correlation with DNA methylation promoters across various tumors. ADAM12 expression strongly linked to ESTIMATE, immune/stromal scores, immune checkpoint genes, tumor mutation burden (TMB), and microsatellite instability (MSI) in specific cancer types. Single-cell and bulk RNA sequencing analysis revealed heightened ADAM12 levels in fibroblasts, highlighting its importance in tumor immunity. Furthermore, the predictive value of immunotherapy surpassed that of tumor mutational burden based on TIDE. Functional enrichment analysis associated ADAM12 with focal adhesion, PI3K-Akt signaling, and ECM-receptor interactions. In vitro experiments confirmed that ADAM12 downregulation significantly impeded proliferation, migration, and invasion of gastric cancer cells. CONCLUSIONS: ADAM12 might be a valuable prognostic biomarker and a promising candidate for tumor immunotherapy.