1. Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education; Key Laboratory of Cancer Prevention and Therapy, Tianjin; State Key Laboratory of Breast Cancer Research, Hexi District, Tianjin, 300060, China
2. 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics
3. Department of Oncology, Southern Research Institute, Birmingham, AL 35205, USA
*These authors contributed equally to this work.
There is an unmet clinical need to identify biomarkers for breast cancer neoadjuvant chemotherapy. Here, using miRNA TaqMan Low-Density Arrays (TLDA), we analyzed the miRNA expression profile in pre-treatment needle aspiration tumor samples from patients who received taxane-anthracycline-based neoadjuvant chemotherapy. Although, in an unsupervised hierarchical cluster analysis, the total miRNA expression profile could not generate a tree with clear distinction between pathologic complete response (pCR) and non-pCR classes, we found that elevated expression of miR-125b and miR-141 was associated with non-pCR. In vitro experiments indicated that inhibition of miR-125b and miR-141 expression reduced cellular survival in response to taxane-anthracycline treatment. Furthermore, co-transfection with miR-125b and miR-141 mimics increased resistance of MCF7 and BT549 cells to taxane-anthracycline induced cytotoxicity. Pathway analyses indicated that many of the target proteins of miR-125b are involved in apoptotic pathways and cell cycle control. Together, we provide evidence that elevated miR-125b and 141 expression predicts a poor clinical responsiveness of taxane-anthracycline-based neoadjuvant chemotherapy.
Keywords: breast cancer, microRNA, neoadjuvant chemotherapy, pathologic complete response, predictive biomarkers.