PURPOSE: Due to the lack of effective screening approaches and early detection biomarkers, ovarian cancer has the highest mortality rates among gynecologic cancers. Herein, we undertook a systematic biomarker discovery and validation approach to identify microRNA (miRNA) biomarkers for the early detection of ovarian cancer. EXPERIMENTAL DESIGN: During the discovery phase, we performed small RNA sequencing in stage I high-grade serous ovarian cancer (n = 31), which was subsequently validated in multiple, independent data sets (TCGA, n = 543; GSE65819, n = 87). Subsequently, we performed multivariate logistic regression-based training in a serum data set (GSE106817, n = 640), followed by its independent validation in three retrospective data sets (GSE31568, n = 85; GSE113486, n = 140; Czech Republic cohort, n = 192) and one prospective serum cohort (n = 95). In addition, we evaluated the specificity of OCaMIR, by comparing its performance in several other cancers (GSE31568 cohort, n = 369). RESULTS: The OCaMIR demonstrated a robust diagnostic accuracy in the stage I high-grade serous ovarian cancer patients in the discovery cohort (AUC = 0.99), which was consistently reproducible in both stage I (AUC = 0.96) and all stage patients (AUC = 0.89) in the TCGA cohort. Logistic regression-based training and validation of OCaMIR achieved AUC values of 0.89 (GSE106817), 0.85 (GSE31568), 0.86 (GSE113486), and 0.82 (Czech Republic cohort) in the retrospective serum validation cohorts, as well as prospective validation cohort (AUC = 0.92). More importantly, OCaMIR demonstrated a significantly superior diagnostic performance compared with CA125 levels, even in stage I patients, and was more cost-effective, highlighting its potential role for screening and early detection of ovarian cancer. CONCLUSIONS: Small RNA sequencing identified a robust noninvasive miRNA signature for early-stage serous ovarian cancer detection.

Center for Gastrointestinal Research; Center for Translational Genomics and Oncology Baylor Scott and White Research Institute and Charles A Sammons Cancer Center Baylor University Medical Center Dallas Texas

Central European Institute of Technology Masaryk University Brno Czech Republic

Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic

Department of Biomedical Sciences City University of Hong Kong Hong Kong P R China

Department of Gynecology Huzhou Maternity and Child Health Care Hospital Huzhou P R China

Department of Laboratory Medicine West China 2nd Hospital Sichuan University Chengdu P R China

Department of Molecular Diagnostics and Experimental Therapeutics Beckman Research Institute of City of Hope Duarte California

Department of Obstetrics and Gynecology Baylor University Medical Center Dallas Texas

Department of Obstetrics and Gynecology Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy West China 2nd University Hospital Sichuan University and Collaborative Innovation Center Chengdu P R China

Department of Translational Genomics University of Southern California Los Angeles California

Masaryk Memorial Cancer Institute Brno Czech Republic

Shenzhen Research Institute City University of Hong Kong Shenzhen P R China

The Sixth Affiliated Hospital of Sun Yat Sen University Guangzhou P R China

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