USP7 overexpression predicts a poor prognosis in lung squamous cell carcinoma and large cell carcinoma.
USP7 overexpression predicts a poor prognosis in lung squamous cell carcinoma and large cell carcinoma.
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USP7 过表达预示着肺鳞状细胞癌和大细胞癌的不良预后。
DOI：
10.1007/s13277-014-2773-4
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发表时间：
2015-03
期刊：
影响因子：
--
通讯作者：
Ding, Jian-Yong
中科院分区：
文献类型：
--
作者：
Zhao, Guang-Yin;Lin, Zong-Wu;Lu, Chun-Lai;Gu, Jie;Yuan, Yun-Feng;Xu, Feng-Kai;Liu, Rong-Hua;Ge, Di;Ding, Jian-Yong
在非小细胞肺癌（NSCLC）中，USP 7表达和p53基因状态均被报道为腺癌患者预后不良的指标;然而，其在肺鳞状细胞癌和大细胞癌中的作用和机制需要澄清。在NSCLC肿瘤（不包括腺癌）、其相应的非肿瘤组织和NSCLC细胞中检查USP 7表达。然后，在110个NSCLC样本（不包括腺癌）中分析USP 7的预后作用。最后，使用特定的vshRNA评估USP 7在NSCLC细胞的增殖、转移和侵袭中的作用和机制。与非肿瘤样品相比，USP 7在NSCLC组织中的表达更高，因此，与HBE细胞相比，在NSCLC细胞系中检测到高水平的USP 7。在USP 7下调后，H460细胞在体外和体内表现出降低的转移/侵袭。初步的机制研究表明，USP 7过表达可能通过诱导MDM 2去泛素化和随后的稳定化，导致Bad磷酸化上调，从而调节p53-MDM 2通路。此外，我们还发现USP 7可以诱导细胞上皮间质转化，从而增强细胞的侵袭能力。临床上，USP 7过表达与恶性表型显著相关。此外，USP 7低患者的5年总生存率高于USP 7高患者。多变量分析显示USP 7过表达是这些癌症的独立预后标志物。USP 7过表达可能调节鳞状细胞癌和大细胞癌细胞的生存和侵袭特性，并可能作为分子靶点。本文的在线版本（doi：10.1007/s13277-014-2773-4）包含补充材料，可供授权用户使用。
In non-small cell lung cancer (NSCLC), both USP7 expression and p53 gene status were reported to be an indicator of poor prognosis in adenocarcinoma patients; however, its roles and mechanisms in lung squamous cell carcinoma and large cell carcinoma need to be clarified. The USP7 expression was examined in NSCLC tumors (excluding adenocarcinoma), their corresponding non-tumorous tissues, and NSCLC cells. Then, the prognostic role of USP7 was analyzed in 110 NSCLC samples (excluding the adenocarcinoma). Finally, the roles and mechanisms of USP7 in the proliferation, metastasis, and invasion of a NSCLC cell were assessed using a specific vshRNA. The USP7 expression was higher in NSCLC tissues compared to non-tumorous samples, accordingly, the high level of USP7 was detected in NSCLC cell lines compared with HBE cell. After the USP7 downregulation, the H460 cells exhibited decreased metastasis/invasion in vitro and in vivo. The preliminary mechanism study indicated overexpression of USP7 might regulate the p53-MDM2 pathway by inducing the MDM2 de-ubiquitination and subsequent stabilization, which resulted in the upregulation of the Bad phosphorylation. Additionally, we also found that USP7 might induce cell epithelial-mesenchymal transition to enhance the cell invasive ability. Clinically, USP7 overexpression significantly correlated with malignant phenotype. Furthermore, the 5-year overall survival in patients with USP7low was higher than that of USP7high. Multivariate analysis showed USP7 overexpression was an independent prognostic marker for these cancers. USP7 overexpression may regulate the survival and invasive properties of squamous cell carcinoma and large cell carcinoma cells, and may serve as a molecular target. The online version of this article (doi:10.1007/s13277-014-2773-4) contains supplementary material, which is available to authorized users.
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