Dynamic changes of miRNA and cancer related proteins (CRPs) expression during neoadjuvant chemotherapy (NAC) for locally advanced breast cancer (LABC).

Abstract

e22099 Background: NAC is used in LABC to downsize the primary tumor and eradicate metastases. This study assessed the Dynamic changes of miRNA and CRP expression during NAC with aim to identify molecular biomarkers that may predict outcome. Methods: Tissue, blood and serum samples were collected at four time points from LABC patients undergoing NAC, including time of diagnosis (base line) after 1st and 4th cycle of Adriamycin/cyclophosphamide, and after 4th cycle of Docetaxel (end point). We used microRNA-microarray for tissue samples and Proximity Ligation Assay (PLA) for serum samples to quantify global miRNA expression and 92 CRPs in LABC patients. The miRNA and CRPS were correlated with clinico-pathological features including stage, grade and clinical response.Statistical analysis was performed using Significant Analysis of Microarray ( SAM), Student's t-test, and Pearson's correlation test. Significant p value was defined as p<0.05. Results: Tissue miRNA expression profiling (n=14) revealed 58 miRNA species that were differentially expressed between NAC endpoint and the baseline (FDR < 15%). Reduced miR-21 expression was associated with disease recurrence. Using PLA (n=33) we identified serumosteoprotegerin, MCP-1, Prolactin, Carbonic Anhydrase IX, CXCL10, CD30L and TGF-alpha levels were significantly associated with overall clinical response (t-test, p<0.05). Moreover, Prolactin and Erythropoietin showed significant associations with the stage (t-test, p<0.05), while MMP3, ErbB4, Midkine, Cathepsin D and Prostasin proteins were associated with the recurrence. Analysis is ongoing to determine the dynamic changes of these biomarkers during the NAC. Conclusions: Our study identified specific miRNAs and CRPs that were differentially expressed during NAC in LABC patients which may have clinical significance.