去泛素化蛋白酶USP37对乳腺癌患者预后的预测价值  

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

作　　者：张琼霞[1] 王希成[1] 陈树鹏[2] 秦鑫添[1] 

机构地区：[1]广东药科大学附属第一医院肿瘤科,广州510080 [2]中山大学肿瘤防治中心、华南肿瘤学国家重点实验室

出　　处：《中华医学杂志》2016年第12期944-948,共5页National Medical Journal of China

基　　金：基金项目：广东省科技计划（2014A020212312）

摘　　要：目的观察分析去泛素化蛋白酶USP37在乳腺癌中表达及其预后的关系。方法应用Western印迹检测USP37在5例乳腺癌新鲜组织中表达情况，采用免疫组织化学检测533例乳腺癌蜡块标本USP37表达并评分。用ROC方法确定USP37表达最佳临界值；检测USP37表达情况与患者临床特征之间相关性。结果USP37免疫组化反应产物主要是定位于细胞质，偶尔见于细胞核，在正常乳腺组织中，USP37低表达或者不表达，而在533例乳腺癌组织标本中，USP37高表达率为50．7％（270／533），低表达或阴性表达率为49．3％（263／533），癌组织中USP37较对应癌旁组织明显高表达。USP37高表达与乳腺癌淋巴结分期、分子分型和增殖标志物Ki67正相关。单因素和多因素分析都表明USP37可以作为乳腺癌总生存（OS）、无复发生存时间（RFS）和无转移生存时间（MFS）独立预后因子。另外，USP37还可以辅助乳腺癌分子分型，预测不同预后亚组。结论USP37在乳腺癌组织中高表达，且过表达USP37可以作为乳腺癌独立预后不良因子。Objective To explore the expression of Ubiquitin-specific processing enzyme 37 （ USP 37） in breast cancer and its association with the prognosis of breast cancer. Methods 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. Results 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. Conclusion Our findings first provide evidences that high expression of USP37 served as an independent molecular biomarker for poor prognosis in breast cancer.

关 键 词：乳腺肿瘤 USP37 肿瘤标志物 

分 类 号：R737.9[医药卫生—肿瘤]