Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.
PLoS One. 2012;7(8):e42540. doi: 10.1371/journal.pone.0042540. Epub 2012 Aug 3.
The significance of ubiquitin-specific protease 22 (USP22) as a potential marker has been growing in the field of oncology. The aim of this study was to investigate the role of USP22 and the association with its potential targets in oral squamous cell carcinoma (OSCC).
Immunohistochemistry was used to determine the expression of USP22 protein in 319 OSCC patients in comparison with 42 healthy controls. The clinical correlations and prognostic significance of the aberrantly expressed protein was evaluated to identify novel biomarker of OSCC.
The incidence of positive USP22 expression was 63.32% in 319 conventional OSCC tissues. The protein expression level of USP22 was concomitantly up-regulated from non-cancerous mucosa to primary carcinoma and from carcinomas to lymph node metastasis (P<0.001). Moreover, statistical analysis showed that positive USP22 expression was positively related to lymph node metastasis, Ki67, Cox-2 and recurrence. Furthermore, it was shown that patients with positive USP22 expression had significantly poorer outcome compared with patients with negative expression of USP22 for patients with positive lymph nodes. Multivariate Cox regression analysis revealed that USP22 expression level was an independent prognostic factor for both overall survival and disease-free survival (P<0.001 and P<0.001, respectively). Cancer cells with reduced USP22 expression exhibited reduced proliferation and colony formation evaluated by MTT and soft agar assays.
To our knowledge, this is the first study that determines the relationship between USP22 expression and prognosis in OSCC. We found that increased expression of USP22 is associated with poor prognosis in OSCC. USP22 may represent a novel and useful prognostic marker for OSCC.
在肿瘤学领域,泛素特异性蛋白酶 22(USP22)作为一种潜在标志物的意义日益凸显。本研究旨在探究 USP22 的作用及其与口腔鳞状细胞癌(OSCC)潜在靶点的关联。
采用免疫组织化学法检测 319 例 OSCC 患者和 42 例健康对照者 USP22 蛋白的表达情况。评估异常表达蛋白的临床相关性和预后意义,以确定 OSCC 的新型生物标志物。
319 例常规 OSCC 组织中,USP22 阳性表达率为 63.32%。USP22 蛋白表达水平从非癌性黏膜到原发性癌再到淋巴结转移呈递增趋势(P<0.001)。此外,统计学分析显示,USP22 阳性表达与淋巴结转移、Ki67、Cox-2 和复发呈正相关。此外,与 USP22 阴性表达患者相比,USP22 阳性表达患者的阳性淋巴结患者预后明显较差。多因素 Cox 回归分析显示,USP22 表达水平是总生存和无病生存的独立预后因素(P<0.001 和 P<0.001)。通过 MTT 和软琼脂实验评估,USP22 表达下调的癌细胞增殖和集落形成能力降低。
据我们所知,这是第一项研究确定了 USP22 表达与 OSCC 预后之间的关系。我们发现,USP22 的表达增加与 OSCC 的不良预后相关。USP22 可能代表 OSCC 一种新的有用的预后标志物。