Ubiquitin specific protease 22 (USP22) is an oncogene that is upregulated in many cancer types, and aberrant expression of USP22 correlates with clinical outcome. However, its potential functional impact in epithelial ovarian cancer (EOC) has not been determined. Here, we report that USP22 was upregulated in EOC specimens and EOC cell lines with important functional consequences. A high level of USP22 in EOC tissues was associated with advanced clinical FIGO stage, lymph node metastasis and worse prognosis. Patients with higher USP22 expression had shorter relapse-free and overall survival. Depletion of USP22 suppressed cell proliferation in vitro and tumor growth in vivo. We found that inhibition of USP22 suppressed cell proliferation by inducing G1 phase cell cycle arrest through synergy with oncogenic transforming growth factor-β1 (TGFB1). Our results indicate that USP22 functions as an oncogene in EOC, and thus USP22 may serve as a potential therapeutic target for individualized EOC treatment.

Abstract. Previous studies have demonstrated that matriptase is involved in degradation of the extracellular matrix and angiogenesis, and is overexpressed in certain forms of epithelial cancer. The present study aimed to examine matriptase expression in ovarian serous adenocarcinoma, and to investigate its association with clinicopathological characteristics and patient prognosis. Matriptase expression was analyzed in 80 ovarian serous adenocarcinoma and 12 normal ovarian tissue samples by immunohistochemistry. All data were analyzed to evaluate the association between matriptase expression and clinicopathological parameters and overall survival. Immunohistochemistry demonstrated that matriptase protein was significantly overexpressed in the ovarian serous adenocarcinoma tissues compared with the normal ovarian tissues (P=0.0003). Furthermore, matriptase expression was significantly associated with clinical stage (P=0.0077) and lymph node metastasis (P=0.0111). Kaplan-Meier survival curves demonstrated that patients with positive matriptase expression had significantly greater survival times (P=0.0008). Matriptase expression is associated with early stage and a greater survival time; therefore, this protein may function as a novel diagnostic and prognostic marker.

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