High claudin-7 expression is associated with a poor response to platinum-based chemotherapy in epithelial ovarian carcinoma

Abstract

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.