Diagnostic potential for a serum miRNA neural network for detection of ovarian cancer
- Brigham and Women's Hospital, United States
- Harvard Medical School, United States
- Medical University of Lodz, Poland
Abstract
Recent studies posit a role for non-coding RNAs in epithelial ovarian cancer (EOC). Combining small RNA sequencing from 179 human serum samples with a neural network analysis produced a miRNA algorithm for diagnosis of EOC (AUC 0.90; 95% CI: 0.81-0.99). The model significantly outperformed CA125 and functioned well regardless of patient age, histology, or stage. Among 454 patients with various diagnoses, the miRNA neural network had 100% specificity for ovarian cancer. After using 325 samples to adapt the neural network to qPCR measurements, the model was validated using 51 independent clinical samples, with a positive predictive value of 91.3% (95% CI: 73.3% - 97.6%) and negative predictive value of 78.6% (95% CI: 64.2% - 88.2%). Finally, biologic relevance was tested using in situ hybridization on 30 pre-metastatic lesions, showing intratumoral concentration of relevant miRNAs. These data suggest circulating miRNAs have potential to develop a non-invasive diagnostic test for ovarian cancer.
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Author details
Dipanjan Chowdhury
Funding
Robert and Deborah First Family Fund
- Kevin M Elias
- Ross S Berkowitz
- Dipanjan Chowdhury
U.S. Department of Defense (OC093426)
- Panagiotis Konstantinopoulos
Honorable Tina Brozman Foundation
- Kevin M Elias
- Dipanjan Chowdhury
U.S. Department of Defense (OC140632)
- Panagiotis Konstantinopoulos
National Institutes of Health (K12HD13015)
- Kevin M Elias
Ruth N White Research Fellowship in Gynecologic Oncology
- Kevin M Elias
- Stephen J Fiascone
Saltonstall Research Fund
- Kevin M Elias
- Stephen J Fiascone
- Ross S Berkowitz
Potter Research Fund
- Kevin M Elias
- Stephen J Fiascone
- Ross S Berkowitz
Sperling Family Fund Fellowship
- Kevin M Elias
- Stephen J Fiascone
- Ross S Berkowitz
Bach Underwood Fund
- Kevin M Elias
- Stephen J Fiascone
- Ross S Berkowitz
First TEAM grant of the foundation for Polish Science and the Smart Growth Operational Programme of the European Union
- Wojciech Fendler
National Institutes of Health (P50CA105009)
- Allison F Vitonis
- Daniel W Cramer
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: All samples were collected after signed informed consent according to locally-approved Institutional Review Board protocols. These studies were approved by the Dana-Farber Cancer Institute Institutional Review Board Protocol 05-060 (NECC study), Brigham and Women's Hospital Institutional Review Board Protocol 2000-P-001678 (Pelvic Mass Protocol), and Dana-Farber/Harvard Cancer Center Institutional Review Board Protocol 12-532 (ERASMOS).
Copyright
© 2017, Elias et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Diagnostic potential for a serum miRNA neural network for detection of ovarian cancer
eLife 6:e28932.
https://doi.org/10.7554/eLife.28932
