Ni Qinggan, Chen Jiahui, Li Xia, Xu Xiaodong, Zhang Nannan, Zhou Ang, Zhou Bin, Lu Qian, Chen Zhong
Department of Hepatobiliary Surgery, Affiliated Hospital, Nantong University, Research Institute of Hepatobiliary Surgery of Nantong University, Nantong 226001, China.
Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Acta Biochim Biophys Sin (Shanghai). 2017 Aug 1;49(8):680-688. doi: 10.1093/abbs/gmx056.
OTUB1 (OTU domain-containing ubiquitin aldehyde binding protein 1) is a deubiquitinating enzyme (DUB) that belongs to the ovarian tumor (OTU) domain protease superfamily. Although it has been demonstrated to play important roles in the development of many kinds of cancer, the mechanism of OTUB1 in hepatocellular carcinoma (HCC) is not clear. The aim of this study was to explore the roles of OTUB1 in HCC progression using cell lines and 115 archived HCC samples. In addition, the clinical outcomes were also analyzed with a special focus on OTUB1 expression in HCC samples. In the immunohistochemical study, OTUB1 showed high expression in 60 of the 115 cases (52.2%). The OTUB1 expression level was significantly correlated with many clinicopathological parameters, including TNM stage (P = 0.002), histology stage (P = 0.002), and metastasis/recurrence (P = 0.016). Survival analysis showed that the group with OTUB1 overexpression had significantly shorter overall survival time than the group with OTUB1 downregulation (hazard ratio [HR] = 0.482; confidence interval [CI]: 0.311-0.748; P = 0.001). Multivariate analysis indicated that OTUB1 expression was a significant and independent prognostic parameter (HR = 0.214; CI: 0.126-0.364; P < 0.001) for HCC patients. The ability of HCC cells to undergo proliferation, migration, and invasion was suppressed by disruption of endogenous OTUB1 using short hairpin RNA (shRNA). OTUB1 expression appears to be a new and independent predictor for the prognosis of HCC patients. Overexpression of OTUB1 in HCC could be a novel, effective, and supplementary biomarker for HCC because it plays a vital role in the progression of HCC.
OTUB1（含OTU结构域的泛素醛结合蛋白1）是一种去泛素化酶（DUB），属于卵巢肿瘤（OTU）结构域蛋白酶超家族。尽管已证明其在多种癌症的发展中起重要作用，但OTUB1在肝细胞癌（HCC）中的作用机制尚不清楚。本研究的目的是使用细胞系和115份存档的HCC样本探索OTUB1在HCC进展中的作用。此外，还分析了临床结果，特别关注HCC样本中OTUB1的表达。在免疫组织化学研究中，OTUB1在115例中的60例（52.2%）中高表达。OTUB1表达水平与许多临床病理参数显著相关，包括TNM分期（P = 0.002）、组织学分期（P = 0.002）和转移/复发（P = 0.016）。生存分析表明，OTUB1过表达组的总生存时间明显短于OTUB1下调组（风险比[HR] = 0.482；置信区间[CI]：0.311 - 0.748；P = 0.001）。多变量分析表明，OTUB1表达是HCC患者的一个显著且独立的预后参数（HR = 0.214；CI：0.126 - 0.364；P < 0.001）。使用短发夹RNA（shRNA）破坏内源性OTUB1可抑制HCC细胞的增殖、迁移和侵袭能力。OTUB1表达似乎是HCC患者预后的一个新的独立预测指标。OTUB1在HCC中的过表达可能是一种新的、有效的和补充性的HCC生物标志物，因为它在HCC进展中起至关重要的作用。
