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    Clinical Relevance of Multidrug Resistance Gene Expression in Ovarian Serous Carcinoma Effusions
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    † Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892
    ‡ Division of Pathology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway;
    § Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, Office of Science Management and Operations, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland
    ∥ Department of Gynecologic Oncology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway
    ⊥ The Medical Faculty, University of Oslo, N-0316 Oslo, Norway
    Laboratory of Cell Biology, National Cancer Institute, 37 Convent Dr., Room 2108, Bethesda, MD 20892. Tel: 301-496-1530. Fax: 301-402-0450. E-mail: [email protected]
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    Molecular Pharmaceutics

    Cite this: Mol. Pharmaceutics 2011, 8, 6, 2080–2088
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    https://doi.org/10.1021/mp200240a
    Published July 15, 2011
    Copyright © 2011 American Chemical Society
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    Abstract

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    The presence of tumor cells in effusions within serosal cavities is a clinical manifestation of advanced-stage cancer and is generally associated with poor survival. Identifying molecular targets may help to design efficient treatments to eradicate these aggressive cancer cells and improve patient survival. Using a state-of-the-art TaqMan-based qRT-PCR assay, we investigated the multidrug resistance (MDR) transcriptome of 32 unpaired ovarian serous carcinoma effusion samples obtained at diagnosis or at disease recurrence following chemotherapy. MDR genes were selected a priori based on an extensive curation of the literature published during the last three decades. We found three gene signatures with a statistically significant correlation with overall survival (OS), response to treatment [complete response (CR) vs other], and progression free survival (PFS). The median log-rank p-values for the signatures were 0.023, 0.034, and 0.008, respectively. No correlation was found with residual tumor status after cytoreductive surgery, treatment (with or without chemotherapy) and stage defined according to the International Federation of Gynecology and Obstetrics. Further analyses demonstrated that gene expression alone can effectively predict the survival outcome of women with ovarian serous carcinoma (OS, log-rank p = 0.0000; and PFS, log-rank p = 0.002). Interestingly, the signature for overall survival is the same in patients at first presentation and those who had chemotherapy and relapsed. This pilot study highlights two new gene signatures that may help in optimizing the treatment for ovarian carcinoma patients with effusions.

    Copyright © 2011 American Chemical Society

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    Supplementary Tables 1–4 including correlation of gene expression profiles with residual tumor status after cytoreductive surgery, with treatment, and with FIGO stage and multidrug resistance-linked gene profiles. This material is available free of charge via the Internet at http://pubs.acs.org.

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    Molecular Pharmaceutics

    Cite this: Mol. Pharmaceutics 2011, 8, 6, 2080–2088
    Click to copy citationCitation copied!
    https://doi.org/10.1021/mp200240a
    Published July 15, 2011
    Copyright © 2011 American Chemical Society
    Request reuse permissions

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