A combination of circulating miRNAs for the early detection of ovarian cancer

// Akira Yokoi 1, 2 , Yusuke Yoshioka 1 , Akihiro Hirakawa 3 , Yusuke Yamamoto 1 , Mitsuya Ishikawa 3 , Shun-ichi Ikeda 3 , Tomoyasu Kato 4 , Kaoru Niimi 2 , Hiroaki Kajiyama 2 , Fumitaka Kikkawa 2 and Takahiro Ochiya 1 1 Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan 2 Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan 3 Statistical Analysis Section, Center for Advanced Medicine and Clinical Research, Nagoya University Graduate School of Medicine, Nagoya, Japan 4 Department of Gynecology, National Cancer Center Hospital, Tokyo, Japan Correspondence to: Takahiro Ochiya, email: tochiya@ncc.go.jp Keywords: circulating microRNAs, ovarian cancer, exosomes, biomarkers, liquid biopsy Received: May 10, 2017 Accepted: July 25, 2017 Published: September 06, 2017 ABSTRACT 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.