USP22 promotes tumor progression and induces epithelial-mesenchymal transition in lung adenocarcinoma
USP22 promotes tumor progression and induces epithelial-mesenchymal transition in lung adenocarcinoma
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USP22 促进肺腺癌的肿瘤进展并诱导上皮间质转化。
DOI：
10.1016/j.lungcan.2015.02.019
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发表时间：
2015-06-01
期刊：
影响因子：
5.3
通讯作者：
Cai, Li
中科院分区：
文献类型：
--
作者：
Hu, Jing;Yang, Dongdong;Cai, Li
目的：我们先前的研究表明USP 22作为癌基因可能介导NSCLC的癌症发生和进展，但其潜在的分子机制仍不清楚。上皮间质转化（EMT）在肿瘤细胞的迁移和侵袭中起重要作用。因此，本研究旨在探讨USP 22在肺腺癌EMT和进展中的作用及其临床意义。方法：采用免疫组织化学方法检测USP 22在临床标本中的表达。通过统计学分析评估异常表达蛋白的临床相关性和预后意义。结果：USP 22在76.03%的肺癌组织中呈阳性表达，且与肺癌的分化程度、T分期和AJCC分期及TGF-β 1表达相关（p = 0.008）。多变量考克斯回归分析显示，USP 22表达水平是总生存期和无病生存期的独立预后因素（HR，2.060; p = 0.013和HR，1.993; p = 0.016）。体外研究表明，USP 22可以调节肺腺癌细胞的增殖和侵袭特性，诱导肺腺癌细胞发生EMT。结论：USP 22可能通过诱导EMT促进肺腺癌细胞的侵袭。(C)2015爱思唯尔爱尔兰有限公司版权所有。
Objectives: Our previous study showed that USP22 as an oncogene may mediate cancer development and progression in NSCLC, but the underlying molecular mechanism remains uncharacterized. Epithelial-mesenchymal transition (EMT) has been reported to play an important role in migration and invasion of the tumor cells. Thus, this study aims to determine the clinical significance and the possible roles of USP22 in EMT and progression of lung adenocarcinoma.Methods: Immunohistochemistry was used to determine the expression of USP22 in clinical samples. The clinical correlations and prognostic significance of the aberrantly expressed proteins were evaluated by statistical analysis. Moreover, we evaluated whether USP22 could induce EMT in cultured lung cancer cells.Results: The USP22 expression was positive in 76.03% of specimens and was correlated with advanced clinicopathologic classifications (differentiation, T and AJCC stages) and TGF-beta 1 expression (p = 0.008). Multivariate Cox regression analysis revealed that USP22 expression level was an independent prognostic factor for both overall survival and disease-free survival (HR, 2.060; p = 0.013 and HR, 1.993; p = 0.016). In vitro study revealed that USP22 can regulate proliferation and invasive properties, and induce EMT of lung adenocarcinoma cells. Moreover, USP22 may up-regulate TGF-beta 1 expression.Conclusions: Our data indicated that USP22 may promote lung adenocarcinoma cell invasion by the induction of EMT. (C) 2015 Elsevier Ireland Ltd. All rights reserved.