Overexpression of ADAM10 correlates with poor prognosis and immune infiltrates in breast cance

Abstract

Abstract Introduction: Breast cancer is still challenging despite advanced therapies. Disintegrin and metalloproteinase 10 (ADAM10) is best known for shedding the extracellular domain of transmembrane proteins, such as Notch, EGFR, HER2, E-cadherin, CD44, thus participating in carcinogenesis. Here, we performed a comprehensive analysis about the clinicopathological features, predictive value of ADAM10 and immune profiles in breast cancer. Methods: ADAM10 genomic, transcriptome, prognostic data, and immune profiles in breast cancer were retrieved from the Oncomine, The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA) and Genotype-Tissue Expression (GTEx) databases. They were analysed with ggpolt2, survminer, GSVA R packages or online tools. Clinical data of breast cancer patients were collected from Huashan Hospital. ADAM10 protein expression was detected by immunohistochemistry. The correlation between clinicopathological characteristics and ADAM10 protein expression were analysed by logistic regression, and prognostic value of ADAM10 were evaluated by Kaplan-Meier method and Cox regression. Results: ADAM10 mRNA was overexpressed in breast cancer compared with normal tissues. Luminal A, luminal B and HER2-enriched subtypes showed higher ADAM10 mRNA levels of than basal-like group. Gene alterations in ADAM10, high mRNA and protein levels of ADAM10 correlate with worse prognosis. HER2-enriched subtype tended to have a favourable OS with low ADAM10 expression. In addition, ADAM10 is associated with specific immune cells (T helper, Tcm, Tem cells, etc) and is positively related to PD-L1. Conclusion: High mRNA and protein expression of ADAM10 is associated with adverse outcome. ADAM10 contributes as an independent prognostic factor and a promising therapeutic target in breast cancer.