Abstract 4786: Circulating miR-21, miR-146a and miR-210 levels in plasma are associated with clinical outcome in breast cancer

Abstract

Abstract Introduction: The discovery of novel non-invasive tumor biomarkers for early diagnosis, prognosis and therapy monitoring remains an undeniable imperative necessity. Circulating miRNAs have recently attracted a lot of interest as novel promising tumor biomarkers. In the present study, we investigated the expression levels of three cancer-associated miRNAs in plasma and evaluated their prognostic significance in breast cancer. Materials and Methods: We examined the expression levels of miR-21, miR-146a and miR-210 in plasma samples of 134 breast cancer patients (57 patients with verified metastasis and 77 patients with operable breast cancer) and 20 healthy individuals. Circulating miRNAs were isolated from 200μL of plasma using mirVana PARIS kit and in each sample 25fmol of the synthetic cel-miR-39 were spiked as exogenous control. For the quantification of plasma miRNAs, a stem-loop cDNA approach and TaqMan real time PCR (LightCycler 2, Roche Applied Science) were used. The normalization procedure was based on a combination of cel-miR-39 as exogenous control and hsa-miR-191 as endogenous control. Relative expression of circulating miRNAs in plasma was evaluated as previously described (Sourvinou et al., J. of Mol. Diagn, 2013). Results: Our results indicate that the expression levels of all three circulating miRNAs are significantly increased in plasma both in operable and metastasis verified breast cancer patients in comparison to those of healthy individuals (p<0.001). The expression levels of plasma miR-210 are slightly increased in patients with operable breast cancer in respect to patients with verified metastasis (p=0.034). In patients with verified metastasis, Kaplan-Meier survival analysis demonstrated an association between elevated levels of plasma miR-21 and overall survival (OS) (p= 0.001) and there was a trend with disease-free interval (DFI) (p=0.053). Concerning miR-146a, increased plasma expression levels were correlated with short OS (p=0.029), but there was no correlation with DFI (p=0.914). Finally, respecting miR-210, Kaplan-Meier survival analysis did not show any association with OS or DFI of these patients. Conclusions: Our results indicate that quantification of circulating miR-21 and miR-146a in plasma are promising prognostic biomarkers in breast cancer and should be further evaluated in a large number of patients. Citation Format: Ioanna S. Sourvinou, Athina Markou, Nikolaos Malamos, Vasilis Georgoulias, Εvi S. Lianidou. Circulating miR-21, miR-146a and miR-210 levels in plasma are associated with clinical outcome in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4786. doi:10.1158/1538-7445.AM2014-4786