Triple negative breast cancer (TNBC) is an aggressive subtype of
breast cancer that is often associated with a poor prognosis. The aim of our study was to identify
biomarkers predictive of TNBC progression. Primary TNBC breast tissue samples including four with
metastasis and six without
metastasis were subjected to Affymetrix GeneChip® analysis (human genome U133).
Ubiquitin-specific protease 2 (USP2) was identified as an upregulated gene in the metastatic group, and its expression was analyzed by immunohistochemistry in 121 primary breast
cancers, 13 paired normal tissues, and 13 paired metastatic lesions. Survival analysis was performed using the log-rank test and Cox regression hazard model.
Matrigel migration and invasion assays in USP2-silenced and USP2-overexpressed
breast cancer cell lines were used to investigate the mechanisms of USP2 in vitro. Positive immunostaining for USP2 was detected in
breast tumors and was correlated with
estrogen receptor (ER) and
progesterone receptor (PR) statuses and TNBC subtype. USP2 was overexpressed in distant metastatic lesions compared with primary breast
cancers. Survival analyses demonstrated that positive USP2 is a poor prognostic factor for disease-free survival. Silencing of USP2 expression decreased migration and invasion in LM2-4175 and SCP46 cells in association with the downregulation of
matrix metalloproteinase-2 (MMP2) expression, whereas overexpression of USP2 in MDA-MB-468 and MDA-MB-231 cells enhanced migration and invasion and upregulated the expression of MMP2. The present study showed that USP2 expression is associated with TNBC cell line's invasiveness and poor survival of
breast cancer patients and may serve as a prognostic
biomarker and therapeutic target for TNBC.