Generation of a Plasma Microrna (Mirna) Signature Predicting Response to Metronomic Chemotherapy (Mc) for Advanced Breast Cancer (Abc)

摘要: ABSTRACT Aim: MC (continuous administration of low doses conventional chemotherapeutics) is characterized by an excellent therapeutic index. In fact, we recently demonstrated that 24% patients with ABC receiving daily dalteparin and oral cyclophosphamide, twice-weekly methotrexate, prednisone (dalCMP) achieved clinical benefit minimal toxicity. While there are no predictive markers response to MC, circulating miRNAs have a high potential serve as easy accessible biomarkers. Hence sought generate plasma miRNA signature dalCMP. Methods: We analyzed pre-treatment samples from top-responders versus dalCMP refractory (n = 6 each) using the nCounter® expression assay (NanoString Technologies). Candidate were validated qRT-PCR. Results: Of 800 human miRBase v18.0, identified 210 expressed in all patient samples. these, average 24 displayed > 2-fold change either direction responders (mean ± SD time tumor progression 65.6 ± 13.9 weeks) non-responders (3.2 ± 1.0 weeks). Student t-testing followed Benjamini–Hochberg correction revealed significantly upregulated non-responders: miR-451a, miR-122-5p, miR-142-3p, miR-548ai, miR-150-5p, miR-342-3p. Using qRT-PCR, confirmed differential pattern miR-548ai. contrast our findings, miR-451a overexpression has been found others exert vitro chemosensitizing properties, whereas miR-142-3p miR-548ai not associated chemosensitivity modulation date. Conclusions: describe first candidate predicting (i.e. dalCMP), currently being original extension study populations 92). This may become helpful tool select suitable for dalCMP, possibly predict other regimens well used types. Disclosure: All authors declared conflicts interest.