Abstract
A major obstacle to improving prognoses in ovarian cancer is the lack of effective screening methods for early detection. Circulating microRNAs (miRNAs) have been recognized as promising biomarkers that could lead to clinical applications. Here, to develop an optimal detection method, we use microarrays to obtain comprehensive miRNA profiles from 4046 serum samples, including 428 patients with ovarian tumors. A diagnostic model based on expression levels of ten miRNAs is constructed in the discovery set. Validation in an independent cohort reveals that the model is very accurate (sensitivity, 0.99; specificity, 1.00), and the diagnostic accuracy is maintained even in early-stage ovarian cancers. Furthermore, we construct two additional models, each using 9–10 serum miRNAs, aimed at discriminating ovarian cancers from the other types of solid tumors or benign ovarian tumors. Our findings provide robust evidence that the serum miRNA profile represents a promising diagnostic biomarker for ovarian cancer.
Highlights
A major obstacle to improving prognoses in ovarian cancer is the lack of effective screening methods for early detection
To focus on extracellular miRNAs released from ovarian cancer cells, we evaluated miRNA expression in extracellular vesicles (EVs), including exosomes, from 12 ovarian cancer cell lines
Based on the optimal level of accuracy, the analysis identified a combination of ten miRNAs that provided the best discrimination in the discovery set [diagnostic index = (0.581) × miR-320a + (0.691) × miR-665 + (−0.704) × miR-3184-5p + (−0.313) × miR-6717-5p + (−1.302) × miR-4459 + (0.729) × miR-6076 + (0.676) × miR3195 + (0.716) × miR-1275 + (0.672) × miR-3185 + (−0.384) × miR-4640-5p—9.375 [model 1]; area under curve (AUC): 1.00; sensitivity: 1.00; specificity: 1.00]
Summary
A major obstacle to improving prognoses in ovarian cancer is the lack of effective screening methods for early detection. To develop an optimal detection method, we use microarrays to obtain comprehensive miRNA profiles from 4046 serum samples, including 428 patients with ovarian tumors. To standardize platforms for collection and detection of serum miRNAs, we recently launched a national project in Japan, entitled Development and Diagnostic Technology for Detection of miRNA in Body Fluids. This project includes the comprehensive characterization of serum miRNA profiles of 13 types of human cancers, including ovarian cancer, in more than 40,000 patients, using the same platform and technology. We describe our identification of promising biomarkers for the diagnosis of ovarian cancer using serum samples obtained from 4046 women, including 428 patients with ovarian tumors. Comprehensive profiles of circulating miRNAs, which were obtained from all samples, enabled us to generate optimal diagnostic models for ovarian cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
