The expression of ubiquitin-specific peptidase 8 and its prognostic role in patients with breast cancer.

ABSTRACT

OBJECTIVES: To clarify the clinical relevance of ubiquitin-specific protease 8 (USP8) for patients with breast cancer (BC). METHODS: Previous BC microarray studies GSE37751, GSE7390, and GSE21653 were reanalyzed to determine the USP8 levels between BC patients and the corresponding normal breast tissues and the correlation between USP8 expression and clinical features and clinical outcomes of patients with BC. Gene set enrichment analysis (GSEA) was conducted to investigate the potential mechanisms. RESULTS: USP8 was downregulated in BC cells compared with that in normal breast tissues (P < 0.0001). The Χ2 test and logistic regression analysis demonstrated that patients in USP8 high-expression group were correlated with better clinical features (including histopathological grading, estrogen receptors, clinical risk group according to Nottingham prognostic index [NPI] criteria and clinical risk group according to Veridex signature) compared with patients in USP8 low-expression group. Kaplan-Meier survival and Cox proportional regression analysis suggested that USP8 predicted better survivals of BC patients in terms of distant metastasis-free survival, time to distant metastasis, disease-free survival, and overall survival. GSEA suggested that USP8 might impact the proliferation of BC cells through several biological processes associated tumorigenesis of BC. USP8 was significantly downregulated in BC patients (P < 0.0001). CONCLUSIONS: Our results demonstrated that USP8 might predict better clinical characteristics and might be a protective factor for patients with BC.