Journal
CLINICAL CANCER RESEARCH
Volume 19, Issue 5, Pages 1213-1224Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-12-2726
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Funding
- UPMC [02.93530]
- Pennsylvania Department of Health and Scaife Foundation
- Department of Defense Ovarian Cancer Academy Award
- NIH/NCI [1 R01 CA163462-01]
- NCI [P30 CA047904]
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Purpose: Endometriosis, a largely benign, chronic inflammatory disease, is an independent risk factor for endometrioid and clear cell epithelial ovarian tumors. Weaimed to identify plasma miRNAs that can be used to differentiate patients with endometriosis and ovarian cancer from healthy individuals. Experimental Design: We conducted a two-stage exploratory study to investigate the use of plasma miRNA profiling to differentiate between patients with endometriosis, patients with endometriosisassociated ovarian cancer (EAOC), and healthy individuals. In the first stage, using global profiling of more than 1,000 miRNAs via reverse transcriptase quantitative PCR (RT-qPCR) in a 20-patient initial screening cohort, we identified 23 candidate miRNAs, which are differentially expressed between healthy controls (n = 6), patients with endometriosis (n = 7), and patients with EAOC (n = 7) based on the fold changes. In the second stage, the 23 miRNAs were further tested in an expanded cohort (n = 88) of healthy individuals (n = 20), endometriosis (n = 33), EAOC(n = 14), and serous ovarian cancer cases (SOC; n = 21, included as controls). Results: We identified three distinct miRNA signatures with reliable differential expression between healthy individuals, patients with endometriosis, and patients with EAOC. When profiled against the control SOC category, our results revealed different miRNAs, suggesting that the identified signatures are reflective of disease-specific pathogenic mechanisms. This was further supported by the fact that the majority of miRNAs differentially expressed in human EAOCs were mirrored in a double transgenic mouse EAOC model. Conclusion: Our study reports for the first time that distinct plasma miRNA expression patterns may serve as highly specific and sensitive diagnostic biomarkers to discriminate between healthy, endometriosis, and EAOC cases. Clin Cancer Res; 19(5); 1213-24. (C) 2013 AACR.
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