High claudin-7 expression is associated with a poor response to platinum-based chemotherapy in epithelial ovarian carcinoma
High claudin-7 expression is associated with a poor response to platinum-based chemotherapy in epithelial ovarian carcinoma
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DOI：
10.1016/j.ejca.2010.11.007
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发表时间：
2011-04-01
影响因子：
8.4
通讯作者：
Bae, Duk-Soo
中科院分区：
文献类型：
--
作者：
Kim, Chul Jung;Lee, Jeong-Won;Bae, Duk-Soo
背景：Claudin-7（CLDN-7）是一种紧密连接蛋白，在多种人类肿瘤中过度表达。我们研究了上皮性卵巢癌（EOC）及其功能作用对卵巢癌细胞系细胞增殖的患者中CLDN-7过表达的预后意义和方法：实时RT-PCR和免疫组化分析71例EOC中CLDN-7的表达进行了评价。我们评估了CLDN-7表达与患者预后的相关性，包括对铂类化疗的敏感性。结果：与正常卵巢组织相比，卵巢上皮性癌组织中CLDN-7基因转录水平显著上调（P <0.001），而卵巢上皮性癌组织中CLDN-7基因转录水平显著上调（P < 0.001）。CLDN-7蛋白在卵巢上皮性癌组织中的表达率为97.1%（69/71），而在正常卵巢组织中无表达（P < 0.001）。原发性肿瘤中CLDN-7的高表达与患者较短的无进展生存期（PFS）（P = 0.005）和对铂类化疗的敏感性差（P = 0.024）相关。CLDN-7在2774和HeyA 8卵巢癌细胞中高表达，siRNA抑制CLDN-7可显著增强2774和HeyA 8卵巢癌细胞对顺铂的敏感性。结论：CLDN-7表达是卵巢癌患者PFS的独立预后因子，可能在调节铂类化疗疗效中发挥作用。(C)2010爱思唯尔有限公司保留所有权利。
Background: Claudin-7 (CLDN-7) is a tight junction protein that has been shown overexpressed in several human cancers. We investigated prognostic significance of CLDN-7 overexpression in patients with epithelial ovarian carcinoma (EOC) and its functional role on cell proliferation in ovarian carcinoma cell lines.Patients and methods: CLDN-7 expression was evaluated by real-time RT-PCR and immunohistochemical analysis in 71 patients with EOC. We assessed the association of CLDN-7 expressions with prognosis of the patients including sensitivity to platinum-based chemotherapy. In vitro experiment was performed with and without inhibition of CLDN-7 by its siRNA to evaluate the sensitivity of the human ovarian cancer cells to cisplatin chemotherapy.Results: CLDN-7 transcripts in EOCs were significantly up-regulated compared with normal ovarian tissues (P < 0.001). The expression of CLDN-7 protein was observed in majority (69/71, 97.1%) of the EOCs but not in normal ovarian tissues (P < 0.001). High CLDN-7 expression in primary tumour correlated with shorter progression-free survival (PFS) of the patients (P = 0.005) and poor sensitivity to platinum-based chemotherapy (P = 0.024). Moreover, CLDN-7 was highly expressed in 2774 and HeyA8 human ovarian cancer cells and inhibition of CLDN-7 by its siRNA significantly enhanced the sensitivity of 2774 and HeyA8 cells to cisplatin treatment.Conclusion: These findings suggest CLDN-7 expression is an independent prognostic factor for PFS and it may play a role in regulating response to platinum-based chemotherapy in the treatment of EOC. (C) 2010 Elsevier Ltd. All rights reserved.