ABSTRACT
Cancer patients who better benefit from neoadjuvant chemotherapy (NeoCh) are those who achieve a successful pathological complete response (pCR) represented by the absence of residual disease. Unfortunately, no highly sensitive and specific tumor biomarkers for predicting the clinical response to NeoCh have yet been defined. The aim of the present study was to ascertain whether miR1455p could discriminate between pCR and nopCR in triplenegative breast cancer patients that received a cisplatin/doxorubicinbased neoadjuvant treatment. miR1455p expression was determined in breast tumors by quantitative RTPCR. Our data showed that miR1455p had a significant low expression (P<0.005) in patients that achieved pCR in comparison to the nonresponder group. Kaplan Meier analysis indicated that low levels of miR1455p were associated with increased diseasefree survival. In addition, receiver operating characteristic (ROC) curve analysis suggested that miR1455p is a good predictor of pCR (P<0.003, AUC=0.7899, 95% CI, 0.63820.9416). Quantitative RTPCR expression analysis also revealed that miR1455p was downregulated in four breast cancer cell lines relative to normal cells. To study the functions of miR1455p, its expression was restored in triplenegative MDAMB231 cells and its effects in cell proliferation were evaluated by MTT assays and in apoptosis using Annexin V experiments. Data revealed that ectopic expression of miR1455p resulted in a significant inhibition of cell proliferation and also induced apoptosis. Moreover, miR1455p led to sensitization of breast cancer cells to cisplatin therapy. In addition, western blot assays indicated that miR1455p downregulated the TGFßR2 protein. In conclusion, miR1455p could be a potential biomarker of clinical response to NeoCh in triplenegative breast cancer. Functionally miR1455p may regulate cell proliferation, at least in part, by targeting TGFßR2.
