A combination of circulating miRNAs for the early detection of ovarian cancer
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Akira Yokoi1,2, Yusuke Yoshioka1, Akihiro Hirakawa3, Yusuke Yamamoto1, Mitsuya Ishikawa3, Shun-ichi Ikeda3, Tomoyasu Kato4, Kaoru Niimi2, Hiroaki Kajiyama2, Fumitaka Kikkawa2 and Takahiro Ochiya1
1Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
2Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan
3Statistical Analysis Section, Center for Advanced Medicine and Clinical Research, Nagoya University Graduate School of Medicine, Nagoya, Japan
4Department of Gynecology, National Cancer Center Hospital, Tokyo, Japan
Takahiro Ochiya, email: [email protected]
Keywords: circulating microRNAs, ovarian cancer, exosomes, biomarkers, liquid biopsy
Received: May 10, 2017 Accepted: July 25, 2017 Published: September 06, 2017
Ovarian cancer is the leading cause of gynecologic cancer mortality, due to the difficulty of early detection. Current screening methods lack sufficient accuracy, and it is still challenging to propose a new early detection method that improves patient outcomes with less-invasiveness. Although many studies have suggested the utility of circulating microRNAs in cancer detection, their potential for early detection remains elusive. Here, we develop novel predictive models using a combination of 8 circulating serum miRNAs. This method was able to successfully distinguish ovarian cancer patients from healthy controls (area under the curve, 0.97; sensitivity, 0.92; and specificity, 0.91) and early-stage ovarian cancer from patients with benign tumors (0.91, 0.86 and 0.83, respectively). This method also enables subtype classification in 4 types of epithelial ovarian cancer. Furthermore, it is found that most of the 8 miRNAs were packaged in extracellular vesicles, including exosomes, derived from ovarian cancer cells, and they were circulating in murine blood stream. The circulating miRNAs described in this study may serve as biomarkers for ovarian cancer patients. Early detection and subtype determination prior to surgery are crucial for clinicians to design an effective treatment strategy for each patient, as is the goal of precision medicine.
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