Abstract

Abstract Purpose Ovarian cancer is usually diagnosed at a late stage, making it the deadliest gynecological cancer in women. Identification of precursor lesions and development of biomarkers for early diagnoses are currently needed. Endometrioid and clear cell ovarian tumors are believed to develop from endometriosis, a largely benign, chronic inflammatory disease. Our purpose is to identify plasma miRNAs that can be used to differentiate ovarian cancer and endometriosis patients from healthy individuals. We hypothesize that plasma miRNAs could serve as biomarkers for minimally invasive detection of endometriosis and endometriosis-associated ovarian cancer (EAOC). Patients and Methods The 20 plasma samples used for initial discovery study include healthy individuals (n=6), endometriosis patients (n=7), and endometriosis associated ovarian cancer patients (n=7). They were used for global profiling of plasma miRNA expression, using probes for more than 1,000 miRNAs. Quantitative PCR (qPCR) analysis of these samples using Quantimir Kit identified 25 candidate miRNAs that can potentially differentiate these three patient categories. For validation of findings with the 25 miRNA candidates, we used additional 69 plasma samples from healthy individuals (n =14), endometriosis (n = 24), endometriosis associated ovarian cancer EAOC (n = 10), and serous ovarian cancer (n= 21, included controls). These samples (n = 89) were subjected to qPCR analyses and their differential gene expression was analyzed by applying several statistical methods. To evaluate the diagnostic power of these miRNAs as potential biomarkers, receiver operating characteristic (ROC) curve and classification models were employed. Results Global profiling of 1150 miRNAs in human plasma by qPCR identified 25 candidate miRNAs. These candidates, when subjected to expanded number of plasma samples revealed a unique signature of miRNAs for reliable identification of endometriosis and ovarian cancer patients. We show that combinations of plasma miRNAs can differentiate between healthy individuals, endometriosis, and EAOC ovarian cancer patients from each other. Conclusion Currently there are no reliable biomarkers for endometriosis and ovarian cancer detection. Our study indicates the significance of blood based miRNA biomarkers that have the potential to serve as highly specific and sensitive diagnostic biomarkers to discriminate between healthy, endometriosis and ovarian cancer individuals. These biomarkers can function as a non-invasive and quick approach for diagnosis. With additional advancement in this area, these miRNAs in combination with other existing biomarkers may prove to be highly accurate predictors of the highly deadly cancer in women. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-479. doi:1538-7445.AM2012-LB-479

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