Abstract
BackgroundMost (70%) epithelial ovarian cancers (EOCs) are diagnosed late. Non-invasive biomarkers that facilitate disease detection and predict outcome are needed. The microRNAs (miRNAs) represent a new class of biomarkers. This study was to identify and validate plasma miRNAs as biomarkers in EOC.Methodology/Principal FindingsWe evaluated plasma samples of 360 EOC patients and 200 healthy controls from two institutions. All samples were grouped into screening, training and validation sets. We scanned the circulating plasma miRNAs by TaqMan low-density array in the screening set and identified/validated miRNA markers by real-time polymerase chain reaction assay in the training set. Receiver operating characteristic and logistic regression analyses established the diagnostic miRNA panel, which were confirmed in the validation sets. We found higher plasma miR-205 and lower let-7f expression in cases than in controls. MiR-205 and let-7f together provided high diagnostic accuracy for EOC, especially in patients with stage I disease. The combination of these two miRNAs and carbohydrate antigen-125 (CA-125) further improved the accuracy of detection. MiR-483-5p expression was elevated in stages III and IV compared with in stages I and II, which was consistent with its expression pattern in tumor tissues. Furthermore, lower levels of let-7f were predictive of poor prognosis in EOC patients.Conclusions/SignificanceOur findings indicate that plasma miR-205 and let-7f are biomarkers for ovarian cancer detection that complement CA-125; let-7f may be predictive of ovarian cancer prognosis.
Highlights
Ovarian cancer is the fifth leading cause of cancer death in women worldwide, and epithelial ovarian cancer (EOC) is the most lethal gynecologic neoplasm [1]
Conclusions/Significance: Our findings indicate that plasma miR-205 and let-7f are biomarkers for ovarian cancer detection that complement Carbohydrate antigen-125 (CA-125); let-7f may be predictive of ovarian cancer prognosis
There was no significant difference in the distribution of Federation of Gynaecology and Obstetrics (FIGO) stages, histologic grade, or CA-125 levels between the training and validation groups (Table 1)
Summary
Ovarian cancer is the fifth leading cause of cancer death in women worldwide, and epithelial ovarian cancer (EOC) is the most lethal gynecologic neoplasm [1]. Because EOC is usually asymptomatic and few screening tests are available, almost 70% of women present with advanced-stage (stage III or IV) disease, with 5-year survival rates of less than 30% [2]. The early detection of EOC may greatly improve clinical outcomes. Non-invasive biomarkers that can facilitate disease detection and staging and predict therapeutic outcome are needed to improve survival rates and determine optimal treatments. Carbohydrate antigen-125 (CA-125) is the most frequently used biomarker for ovarian cancer detection [4], but it is only elevated in approximately 50% of stage I EOCs and 70%–90% of advanced cases [5]. Most (70%) epithelial ovarian cancers (EOCs) are diagnosed late. Non-invasive biomarkers that facilitate disease detection and predict outcome are needed. This study was to identify and validate plasma miRNAs as biomarkers in EOC
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