Zeng Zhi, Wu Hong-Xue, Zhan Na, Huang Ya-Bing, Wang Ze-Sheng, Yang Gui-Fang, Wang Ping, Fu Guo-Hui
Pathology Center, Shanghai First People`s Hospital / Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Number 280, South Chong-Qing Road, Shanghai, 200025, China,
Tumour Biol. 2014 Apr;35(4):3845-53. doi: 10.1007/s13277-013-1509-1. Epub 2013 Dec 17.
Ubiquitin-specific protease 10 (USP10), a novel deubiquitinating enzyme, had been associated with growth of tumor cell. However, the role of USP10 in gastric cancer carcinogenesis had not been elucidated yet. The aim of this study was to investigate the expression level of USP10 in gastric carcinoma (GC) tissues and cell lines, then to evaluate the clinical significance of USP10 in GC patients. USP10, E-cadherin, Ki67 and p53 expressions were detected in 365 GC and 40 non-cancerous mucosa tissues by immunohistochemistry. Western blot for USP10 was performed on additional fresh GC tissues and GC cell lines. The expression level of USP10 in GC tissues was proved lower than that in non-cancerous mucosa tissues (p < 0.05). It was also lower in GC cell lines (AGS, BGC-823 and MKN45 cells) than that in gastric epithelial immortalized cell line (GES-1). Clinicopathological analysis showed that USP10 expression was negatively correlated with gastric wall invasion (p = 0.009), nodal metastasis (p = 0.002), and TNM stage (p = 0.000). In contrast, a positively correlation between the expression of USP10 and E-cadherin was found (p < 0.05), but there was no relationship proved between Ki67, p53 and USP10 (p > 0.05). On the Kaplan-Meier survival curves, we found poor prognosis in GC patients was associated with negative USP10 expression (p < 0.05). Moreover, USP10 expression was an independent prognostic factor for the overall survival in multivariate analysis. Our findings suggested that USP10 was an independent predictor of prognosis of GC patients.
泛素特异性蛋白酶10(USP10)是一种新型去泛素化酶,与肿瘤细胞的生长有关。然而,USP10在胃癌发生中的作用尚未阐明。本研究旨在探讨USP10在胃癌(GC)组织和细胞系中的表达水平,进而评估USP10在GC患者中的临床意义。采用免疫组织化学法检测365例GC组织和40例非癌黏膜组织中USP10、E-钙黏蛋白、Ki67和p53的表达。对另外的新鲜GC组织和GC细胞系进行USP10的蛋白质印迹分析。结果表明,GC组织中USP10的表达水平低于非癌黏膜组织(p<0.05)。在GC细胞系(AGS、BGC-823和MKN45细胞)中其表达也低于胃上皮永生化细胞系(GES-1)。临床病理分析显示,USP10表达与胃壁浸润(p = 0.009)、淋巴结转移(p = 0.002)和TNM分期(p = 0.000)呈负相关。相反,发现USP10表达与E-钙黏蛋白呈正相关(p<0.05),但未证实Ki67、p53与USP10之间存在相关性(p>0.05)。在Kaplan-Meier生存曲线上,我们发现GC患者预后不良与USP10表达阴性有关(p<0.05)。此外,在多因素分析中,USP10表达是总生存的独立预后因素。我们的研究结果表明,USP10是GC患者预后的独立预测因子。