Background and purpose: Herpesvirus-associated ubiquitin-specific protease (HAUSP) is a new deubiquitinating enzyme that was recently discovered. It has been demonstrated that HAUSP could deubiquitinate p53 both in vitro and in vivo. These results suggested that HAUSP might act as a tumor suppressor through the stabilization of p53 protein. The aim of this study was to investigate the expression of HAUSP in breast carcinoma, and its association with p53 protein as well as their relationship to prognosis. Methods: The expression of HAUSP mRNA was detected by real-time PCR. HAUSP protein and p53 protein were detected by immunohistochemistry with EnVision system in breast carcinoma tissues and noncancerous tissues. The relationship between their expressions and clinical pathological parameters were analyzed. Results: The expression of HAUSP mRNA was significantly lower in breast cancer tissue than noncancerous tissue (1.85±0.04 vs. 2.74±0.03, P<0.01). The positive rates of HAUSP protein were significantly lower in breast cancer tissue in noncancerous tissue (59.4% vs. 75.0%, P<0.01), and expression of HAUSP protein had no significant correlation with the clinical pathological parameters. There was no significant correlation between HAUSP and p53 protein (P>0.05). The expression of HAUSP mRNA was positively associated with that of HAUSP protein (P<0.01). There was no significant correlation between HAUSP and p53 protein. DFS of patients with both HAUSP positive and p53 negative was significant higher than the controls (P<0.01). Conclusion: Down-regulation of HAUSP protein and HAUSP mRNA in breast carcinoma indicated that HAUSP gene might correlated to tumor carcinogenesis. In addition, the simultaneous evaluation of both HAUSP expression and p53 expression status may be helpful to evaluate the prognosis of breast cancer patients.%背景与目的:疱疹病毒相关性泛素特异性蛋白酶(herpesvirus-associated ubiquitin specific protease,HAUSP)是新近发现的一种去泛素化蛋白酶.最近的研究表明,HAUSP能在体内外使p53去泛素化,避免其降解,提示HAUSP可能通过稳定p53蛋白发挥胜瘤抑制功能.本研究旨在观察HAUSP在乳腺癌组织及非癌组织中表达的差异;探讨HAUSP与p53蛋白表达的相关性及其与乳腺癌预后的关系.方法:采用实时荧光定量-PCR检测13例新鲜乳腺癌组织及13例癌旁组织中HAUSP mRNA的表达;免疫组织化学EnVision法检测69例乳腺痛组织和40例非癌组织以及13例新鲜乳腺癌组织中HAUSP蛋白及p53蛋白的表达.结合患者临床资料进行预后分析.结果:乳腺癌组织中HAUSP mRNA转录量为1.85±0.04,癌旁组织为2.74±0.03,HAUSP mRNA在乳腺癌中的转录量明显低于癌旁组织,差异有显著性(P<0.01).ItAUSP蛋白在乳腺癌及对照组中的阳性表达率分别为59.4%和75.0%,乳腺痛组织阳性率低于对照组,差异有显著性(P<0.01);HAUSP蛋白表达与患者的年龄、瘤体大小、分化程度、病理类型、腋窝淋巴结转移及临床分期均无相关性;HAUSP蛋白表达与其mRNA转录一致;HAUSP mRNA和其蛋白的表达与p53蛋白的表达无相关性(P>0.05);同时具备HAUSP蛋白阳性和p53蛋白阴性的乳腺癌患者无病生存率(disease-free survival,DFS)高于HAUSP蛋白阴性或p53阳性的患者.结论:乳腺癌HAUSPmRNA和蛋白表达下调提示删USP基因可能与乳腺癌发生、发展有关.同时评价HAUSP蛋白和p53蛋白的状态可能有助于判断患者的预后.
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