Expression of USP7 and MARCH7 Is Correlated with Poor Prognosis in Epithelial Ovarian Cancer.
Expression of USP7 and MARCH7 Is Correlated with Poor Prognosis in Epithelial Ovarian Cancer.
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DOI：
10.1620/tjem.239.165
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发表时间：
2016-07
期刊：
影响因子：
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通讯作者：
Li Zhang;Hua Wang;Lin Tian;Haixia Li
中科院分区：
文献类型：
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作者：
Li Zhang;Hua Wang;Lin Tian;Haixia Li
上皮性卵巢癌(EOC)是女性最严重的恶性肿瘤之一，由于转移迅速，缺乏理想的生物标志物，总体生存率较低。泛素特异性蛋白水解酶7(USP7)是一种重要的去泛素化酶，据报道在包括肝癌、前列腺癌和结肠癌在内的多种癌症中表达上调。膜相关环-CH蛋白7(March7)属于E3泛素连接酶的成员。此外，March7还调节T细胞的增殖和神经元的发育，并参与膜转运和蛋白质降解。重要的是，March7本身是泛素化的，是USP7的潜在底物。然而，USP7和March7在EoC中的作用仍有待研究。收集卵巢癌患者121例，采用免疫组织化学方法检测USP7和March7在肿瘤组织中的表达水平。我们发现这两种蛋白的高表达与卵巢癌患者的淋巴结转移有关。单因素和多因素分析显示，两种蛋白高表达的患者预后较差。随后，利用SKOV3人卵巢腺癌细胞，我们发现USP7和March7都增强了细胞的增殖和侵袭能力。此外，USP7还可通过MARCH7信号通路调节E-钙粘蛋白和β-连环蛋白的表达水平。我们的研究结果表明，USP7和March7参与了EOC的发生发展。总之，分析USP7和March7的表达对预测EOC的预后有较高的预后价值。
Epithelial ovarian cancer (EOC) is one of the worst malignancies in females with poor overall survival due to the rapid metastasis and the absence of ideal biomarkers. Ubiquitin-specific protease 7 (USP7), an important deubiquitinating enzyme, was reported to be upregulated in several cancers, including liver, prostate and colon cancers. Membrane associated RING-CH protein 7 (MARCH7) belongs to the member of the E3 ubiquitin ligases. In addition, MARCH7 regulates T cell proliferation and the neuronal development and participates in the membrane trafficking and protein degradation. Importantly, MARCH7 itself is ubiquitinated and acts as a potential substrate of USP7. However, the roles of USP7 and MARCH7 in EOC remain to be investigated. We collected 121 EOC patients and analyzed the expression levels of USP7 and MARCH7 in tumor tissues with immunohistochemical staining. We found that the high expression of the two proteins was correlated with lymph node metastasis in EOC patients. Univariate and multivariate analyses revealed that the patients with high expression of the two proteins showed poorer prognosis compared with other patients. Subsequently, using SKOV3 human ovarian adenocarcinoma cells, we showed that either USP7 or MARCH7 enhanced the proliferation and invasion abilities. Moreover, USP7 could regulate the expression levels of E-cadherin and β-catenin through the MARCH7 signaling pathway. Our findings indicate that USP7 and MARCH7 are involved in the progression of EOC. In conclusion, analyzing the expression of USP7 and MARCH7 has high prognostic value in predicting EOC prognosis.