Integrated extracellular microRNA profiling for ovarian cancer screening.

Yokoi A1,2, Matsuzaki J1, Yamamoto Y1, Yoneoka Y3, Takahashi K3, Shimizu H3, Uehara T3, Ishikawa M3, Ikeda SI3, Sonoda T1, Kawauchi J4, Takizawa S4, Aoki Y5, Niida S6, Sakamoto H7, Kato K8, Kato T3, Ochiya T9.

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Abstract

A major obstacle to improving prognoses in ovarian cancer is the lack of effective screening methods for early detection. Circulating microRNAs (miRNAs) have been recognized as promising biomarkers that could lead to clinical applications. Here, to develop an optimal detection method, we use microarrays to obtain comprehensive miRNA profiles from 4046 serum samples, including 428 patients with ovarian tumors. A diagnostic model based on expression levels of ten miRNAs is constructed in the discovery set. Validation in an independent cohort reveals that the model is very accurate (sensitivity, 0.99; specificity, 1.00), and the diagnostic accuracy is maintained even in early-stage ovarian cancers. Furthermore, we construct two additional models, each using 9-10 serum miRNAs, aimed at discriminating ovarian cancers from the other types of solid tumors or benign ovarian tumors. Our findings provide robust evidence that the serum miRNA profile represents a promising diagnostic biomarker for ovarian cancer.