Circulating miR-200c-3p as a marker of metastatic disease at diagnosis in breast cancer patients.

Abstract

e12559 Background: MicroRNAs are involved in cancer biology through their role in regulation of protein expression. The miR-200 family plays a dual role in breast cancer (BC), both regulating epithelial to mesenchymal transition and promoting metastatic colonization. Plasma levels of miR-200 have been previously evaluated as prognostic factors in early and metastatic BC (MBC) but its role as a potential diagnostic marker is less well established. The aim of this study was to determine the potential diagnostic value of miR-200c-3p plasmatic levels in women with locally advanced and metastatic BC. Methods: We included 73 BC patients and 14 controls. Plasma samples were obtained at diagnosis, before treatment. RNA from plasma samples was extracted with NucleoSpin miRNA plasma (Macherey-Nagel). We analyzed expression levels of miR-200c-3p, which were relativized (2-ΔΔCT method) to miR-16. Non-parametric statistical tests were used to determine the association of miR-200c levels with clinical variables. Receiver-operating curves (ROC) were constructed and diagnostic ability evaluated. Kaplan-Meier curves and Cox models were used for survival analyses. Results: 73 BC patients were included: 36 locally advanced BC (LABC) and 37 MBC (7 recurrences and 30 MBC at initial diagnosis [MBCID]). Plasma miR-200c levels were significantly higher in MBC than in controls (p = 0.001) and in LABC (p = 0.001). We found differences neither for age nor for estrogen receptors, HER2, tumor subtype or histology. Overall and disease free survival did not differ by miR-200c levels in any of the groups. Among MBC patients, higher levels were observed in MBCID (p = 0.023). In the group of women with an initial diagnosis of BC (n = 65), high miR-200c levels (over 1st tertile) identified metastatic disease with a sensitivity of 90.0% (95%CI: 72.3-97.4%) and a specificity of 51.4% (95%CI: 34.3-68.3%); negative predictive value: 85.7%; positive predictive value: 61.4%; ROC AUC: 0.79. Conclusions: MiR-200c plasma levels are higher in BC patients with metastatic disease at diagnosis, and might be clinically useful to identify them. Further research on miR200c biological role in MBC and validation in larger populations with sequential samples are warranted.