Elevated expression of USP22 in correlation with poor prognosis in patients with invasive breast cancer

Abstract

Purpose: Ubiquitin-specific protease 22 (USP22), a novel deubiquitinating enzyme, has been associated with metastasis, therapy resistance, and cell-cycle progression. The purpose of this study was to investigate the expression level of USP22 in breast samples and to evaluate its clinical significance in breast cancer patients.

Methods: Immunohistochemistry was used to determine the expression of USP22 protein in 31 breast fibroadenoma and 100 breast cancer patients in comparison with 34 normal breast specimens. Furthermore, we analyzed the correlation between the expression of the USP22 protein and various clinicopathologic factors including survival status of patients with breast cancer.

Results: The immunohistochemistry results showed that the expression level of USP22 protein in breast cancer samples was significantly higher than that in breast fibroadenoma and normal breast tissues (P = 0.003 and P = 0.021). Moreover, statistical analysis showed that high USP22 expression was positively related to lymph node metastasis, Her-2, Ki67, and recurrence. Furthermore, it was shown that patients with high USP22 expression had significantly poorer outcome compared with patients with low expression of USP22 for patients with positive lymph nodes. Multivariate Cox regression analysis revealed that USP22 expression level was an independent prognostic factor for both overall survival and disease-free survival (P = 0.039 and P = 0.041, respectively).

Conclusion: Overexpression of USP22 may contribute to the progression of breast cancer and thus may serve as a new molecular marker to predict the prognosis of breast cancer patients.

Fig. 1

Immunohistochemical staining of USP22 protein in breast specimens a high USP22 expression in invasive ductal breast cancer tissues; b, c low USP22 expression in breast fibroadenomas and normal breast specimens, respectively; d Negative control slide with PBS was not positively stained in breast cancer tissues

Fig. 2

Kaplan–Meier curves of the overall survival (OS) and disease-free survival (DFS) for the invasive breast cancer patients with high and low USP22 expression. P values were obtained by log-rank test. a OS curves of breast cancer patients according to the USP22 immunostaining; b DFS curves of breast cancer patients according to the USP22 immunostaining

Fig. 3

The overall survival curves are significantly separated in different lymph node status (LN). a Patients with positive lymph node (LN+); b patients with negative lymph node (LN−)

Fig. 4

Result of overall survival analyses based on histology grade in patients with low USP22 expression