Circulating miRNAs are promising biomarkers in oncology but have not yet been implemented in the clinic given the lack of concordance across studies. In order to increase the cross‐studies reliability, we attempted to reduce and to control the circulating miRNA expression variability between patients. First, to maximize profiling signals and to reduce miRNA expression variability, three isolation kits were compared and the NucleoSpin® kit provided higher miRNA concentrations than the other widely used kits. Second, to control inter‐sample variability during the profiling step, the exogenous miRNAs normalization method commonly used for RT‐qPCR validation step was adapted to microarray experiments. Importantly, exogenous miRNAs presented two‐fold lower inter‐sample variability than the widely used endogenous miR‐16‐5p reflecting that the latter is subject to both biological and technical variability. Although Caenorhabditis elegans miRNAs isolation yields were heterogeneous, they correlated to each other and to their geometrical mean across samples. The normalization based on the geometrical mean of three exogenous miRNAs increased the correlation up‐to 0.97 between the microarrays and individual RT‐qPCR steps of circulating miRNAs expression. Overall, this new strategy open new avenue to identify reliable circulating miRNA signatures for translation into clinical practice.

Ovarian cancer (OC) is the second most common and the most lethal of the gynecological malignancies. Currently, there exists no effective screening tool for OC. MicroRNAs (miRNAs) are endogenous 18-23 nucleotide non-coding RNAs that refine gene expression. MiRNAs have been found to be aberrantly expressed in OC tumor tissue as well as detectable in biological fluids such as the blood, urine, and ascites and have been proposed as biomarkers and therapeutic targets for OC. Areas covered: This review summarizes the current knowledge regarding the application of miRNAs as diagnostic, prognostic, and predictive biomarkers in OC. It describes the various tissues allowing for the analysis of miRNAs such as tumor tissue, blood, ascites and urine. It also highlights the potential of miRNAs as a therapy in other cancers and how these therapies may be applied to ovarian cancer. Expert opinion: The study of miRNAs is an innovative and promising field for the diagnosis and treatment of ovarian cancer. Methodological issues surrounding their detection and application therapeutically remain, such as the study of various OC histotypes within the same cohort, the choice of 'normal tissue' for comparison and the difficulties surrounding the choice of a normalization miRNA.