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MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer

  • Douglas D. Taylor
    Correspondence
    Corresponding author. Division of Gynecologic Oncology, University of Louisville School of Medicine, 511 S. Floyd Street, MDR 420, Louisville, KY 40202, USA.
    Affiliations
    Department of Obstetrics, Gynecology, and Women’s Health, University of Louisville School of Medicine, Louisville, KY, USA
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  • Cicek Gercel-Taylor
    Affiliations
    Department of Obstetrics, Gynecology, and Women’s Health, University of Louisville School of Medicine, Louisville, KY, USA
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      Abstract

      Objectives

      Most ovarian cancer patients are diagnosed at an advanced stage (67%) and prospects for significant improvement in survival reside in early diagnosis. While expression patterns of a recently identified biomarker family, microRNA, appear to be characteristic of tumor type and developmental origin, microRNA profiling has been limited to tissue specimens. Tumors actively release exosomes into the peripheral circulation and we now demonstrate the association of microRNAs with circulating tumor-derived exosomes.

      Methods

      Circulating tumor exosomes were isolated using a modified MACS procedure with anti-EpCAM. Initially, microRNA profiles of ovarian tumors were compared to those of tumor exosomes isolated from the same patients. Levels of 8 microRNAs (miR-21, miR-141, miR-200a, miR-200c, miR-200b, miR-203, miR-205 and miR-214) previously demonstrated as diagnostic, were compared in exosomes isolated from sera specimens of women with benign disease and various stages of ovarian cancer.

      Results

      MicroRNA from ovarian tumor cells and exosomes from the same patients were positive for 218 of 467 mature microRNAs analyzed. The levels of the 8 specific microRNAs were similar between cellular and exosomal microRNAs (exhibiting correlations from 0.71 to 0.90). While EpCAM-positive exosomes were detectable in both patients with benign ovarian disease and ovarian cancer, exosomal microRNA from ovarian cancer patients exhibited similar profiles, which were significantly distinct from profiles observed in benign disease. Exosomal microRNA could not be detected in normal controls.

      Conclusions

      These results suggest that microRNA profiling of circulating tumor exosomes could potentially be used as surrogate diagnostic markers for biopsy profiling, extending its utility to screening asymptomatic populations.

      Keywords

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