Predictive value of deubiquitination enzymes USP37 in the prognosis of breast cancer

Abstract

To explore the expression of Ubiquitin-specific processing enzyme 37(USP 37)in breast cancer and its association with the prognosis of breast cancer. In this study, the method of Western blot was utilized to examine the expression of USP37 protein in breast cancer fresh tissue. Immunohistochemistry (IHC) was used to determine the expression of USP37 in 533 cases of breast cancer. Receive operating characteristic (ROC) curve analysis was employed to determine a cut-off score for USP37 expression. For validation, the ROC-derived cut-off score was subjected to analysis the association of USP37 expression with cancer patient outcome and clinical characteristics. USP37 protein was mainly located in cytoplasm of the cell, occasionally in nucleus by immunohistochemistry. In the normal breast tissue, USP37 was not expressed or with low expression level, while in the 533 cases of breast cancer, the high USP37 expression was detected in 50.7% samples (270/533) with corresponding low or negative expression rate 49.3% (263/533). We found that USP37 was highly expressed in primary breast cancer tissues compared to paired adjacent non-cancerous tissues. High expression of USP37 was associated with breast cancer node classification, molecular classification and proliferation biomarker Ki67. Both univariate and multivariate analyses further revealed that USP37 expression was an independent poor prognostic parameter for overall survival (OS), recurrence-free survival (RFS) and metastasis-free survival (MFS) in breast cancer. Furthermore, USP37 expressions divided the luminal and triple negative breast cancer into different prognosis subgroups. Our findings first provide evidences that high expression of USP37 served as an independent molecular biomarker for poor prognosis in breast cancer.