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Identification of an ovarian clear cell carcinoma gene signature that reflects inherent disease biology and the carcinogenic processes

Oncogene volume 29, pages 1741–1752 (2010)Cite this article

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Abstract

Ovarian clear cell carcinoma (OCCC) shows unique clinical features including an association with endometriosis and poor prognosis. We previously reported that the contents of endometriotic cysts, especially high concentrations of free iron, are a possible cause of OCCC carcinogenesis through iron-induced persistent oxidative stress. In this study, we conducted gene expression microarray analysis using 38 ovarian cancer cell lines and identified genes commonly expressed in both OCCC cell lines and clinical samples, which comprise an OCCC gene signature. The OCCC signature reproducibly predicts OCCC specimens in other microarray data sets, suggesting that this gene profile reflects the inherent biological characteristics of OCCC. The OCCC signature contains known markers of OCCC, such as hepatocyte nuclear factor-1β (HNF-1β) and versican (VCAN), and other genes that reflect oxidative stress. Expression of OCCC signature genes was induced by treatment of immortalized ovarian surface epithelial cells with the contents of endometriotic cysts, indicating that the OCCC signature is largely dependent on the tumor microenvironment. Induction of OCCC signature genes is at least in part epigenetically regulated, as we found hypomethylation of HNF-1β and VCAN in OCCC cell lines. This genome-wide study indicates that the tumor microenvironment induces specific gene expression profiles that contribute to the development of distinct cancer subtypes.

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan

    K Yamaguchi, M Mandai, N Matsumura, J Hamanishi, T Baba & I Konishi

  2. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA

    K Yamaguchi & S K Murphy

  3. Department of Biostatistics, Graduate School of Public Health, Kyoto University, Sakyo-ku, Kyoto, Japan

    T Oura

  4. Department of Data Science, Research Organization of Information and Systems, The Institute of Statistical Mathematics, Tachikawa, Tokyo, Japan

    S Matsui

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  1. K Yamaguchi
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Correspondence to M Mandai.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Yamaguchi, K., Mandai, M., Oura, T. et al. Identification of an ovarian clear cell carcinoma gene signature that reflects inherent disease biology and the carcinogenic processes. Oncogene 29, 1741–1752 (2010). https://doi.org/10.1038/onc.2009.470

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