Abstract
Abstract Background: Ovarian cancer is the fifth leading cause of cancer death in women worldwide. While the survival rates of women with early stage ovarian cancer are high, most cases are diagnosed late. Due to asymptomatic development and few screening options, almost 70% of women present at late stages of carcinogenesis. Sensitive, non-invasive biomarkers that can facilitate disease detection, staging and prediction of therapeutic outcome are highly desirable to improve survival rate and help to determine optimized treatment for ovarian cancer. The small non-coding RNAs, microRNAs (miRNAs), have recently been identified as critical regulators for various diseases including cancer and may represent a novel class of cancer biomarkers. The purpose of this study was to identify and validate circulating microRNAs in human plasma for use as such biomarkers in ovarian cancer. Methods/ Principle findings: We scan the circulating plasma miRNAs by Taqman Low Density Array, then identify and validated 30 markers in plasma samples among 70 cases and 70 controls by real-time PCR assay. Promising associations were evaluated in a second stage, comprising 150 cases and 150 controls. We found that compared with normal, there are 9 miRNAs (miR-205, miR-200a, miR-184, miR-34a*, miR-141, miR-483-5p, miR-193b*, let-7e*, miR-363*) expressed higher in ovarian cancer group, while the miR-98 and let-7f have the lower levels in ovarian cancer. Compared with early stage cases (stage I), there is only miR-483-5p expressed higher in advanced stages (stage II-IV). Receiver operating characteristic (ROC) analysis was used to evaluate the sensitivity and specificity of candidate plasma microRNA markers. We observed that combination of these identified miRNAs and CA-125, a widely used marker for ovarian cancer, further improved the accuracy of detection. Furthermore, our analysis showed that high levels of plasma miR-483-5p or low levels of let-7f predicted poor prognosis of ovarian cancer patients, consistent with the expression of miRNAs in ovarian cancer tissues. Conclusions/Significance: We propose that plasma miRNAs (miR-205, miR-200a, miR-184, miR-34a*, miR-141, miR-483-5p, miR-193b*, let-7e*, miR-363*) are potential biomarkers that complements CA-125 in detecting ovarian cancer; miR-483-5p and let-7f may predict the prognosis of ovarian cancer. It may provide new avenues for the detection, diagnosis, and therapy of this deadly disease. 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 4135. doi:1538-7445.AM2012-4135
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