Clinical significance of Keap1 and Nrf2 in oral squamous cell carcinoma.
Clinical significance of Keap1 and Nrf2 in oral squamous cell carcinoma.
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Keap1和Nrf2在口腔鳞状细胞癌中的临床意义
DOI：
10.1371/journal.pone.0083479
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sun ZJ
中科院分区：
文献类型：
--
作者：
Huang CF;Zhang L;Ma SR;Zhao ZL;Wang WM;He KF;Zhao YF;Zhang WF;Liu B;Sun ZJ
氧化应激已被报道在各种癌症的进展和复发中起重要作用。然而，氧化应激标志物Keap 1和Nrf 2在口腔鳞状细胞癌（OSCC）中的作用和临床意义尚未阐明。本研究旨在利用组织芯片技术研究氧化应激标志物Keap 1和Nrf 2在口腔鳞癌中的表达及其与口腔鳞癌病理特征的关系。应用免疫组织化学方法对17例正常口腔黏膜、7例口腔上皮异常增生和43例口腔鳞癌组织芯片进行研究。分析这些蛋白与病理特征的关系。氧化应激标志物Keap 1、Nrf 2和抗氧化剂PPIA、Prdx 6以及CD 147的表达从正常口腔黏膜到OSCC依次增加，且Keap 1、Nrf 2、PPIA、Prdx 6和CD 147在OSCC中的表达显著高于正常口腔黏膜。Keap 1、Nrf 2在肿瘤中的表达与T分期、淋巴结转移、病理分级无关。此外，我们检查了这些氧化应激标志物之间的关系，发现Keap 1与Nrf 2，Prdx 6和CD 147显著相关。Nrf 2和Prdx 6之间也存在显著的相关性。Kaplan-Meier分析发现Keap 1和Nrf 2过表达的患者总生存期并没有显著降低。这些结果表明，活性氧标志物与口腔鳞癌的发生和发展有关，可能具有预后价值，并可能被视为潜在的治疗靶点。
Oxidative stress has been reported to play an important role in progression and prognostication in various kinds of cancers. However, the role and clinical significance of oxidative stress markers Keap1 and Nrf2 in oral squamous cell carcinoma (OSCC) has not been elucidated. This study aimed to investigate the correlation of oxidative stress markers Keap1 and Nrf2 expression and pathological features in OSCC by using tissue microarray. Tissue microarrays containing 17 normal oral mucosa, 7 oral epithelial dysplasia and 43 OSCC specimens were studied by immunohistochemistry. The association among these proteins and pathological features were analyzed. Expression of oxidative stress markers Keap1, Nrf2, and antioxidants PPIA, Prdx6, as well as CD147 was found to increase consecutively from normal oral mucosa to OSCC, and the Keap1, Nrf2, PPIA, Prdx6, CD147 expression in OSCC were significantly higher when compared to normal oral mucosa. Expression of Keap1, Nrf2 in tumors was not found to be significantly associated with T category, lymph node metastases, and pathological grade. Furthermore, we checked the relationship among these oxidative stress markers and found that Keap1 was significantly correlated with Nrf2, Prdx6 and CD147. Significant relationship between Nrf2 and Prdx6 was also detected. Finally, we found patients with overexpression of Keap1 and Nrf2 had not significantly worse overall survival by Kaplan–Meier analysis. These findings suggest that ROS markers are associated with carcinogenesis and progression of OSCC, which may have prognostic value and could be regarded as potential therapeutic targets in OSCC.
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DOI：
10.1002/hed.20430
发表时间：
2006-09-01
影响因子：
2.9
作者：
Stacy, Donnie R.;Ely, Kim;Freeman, Michael L.
通讯作者：
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影响因子：
11.2
作者：
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DOI：
10.1158/1078-0432.ccr-09-3352
发表时间：
2010-07-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
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通讯作者：
Wistuba II
影响因子：
254.7
作者：
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通讯作者：
Pisani, P
影响因子：
30.8
作者：
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通讯作者：
Yamamoto, M