Cross-platform genomic identification and clinical validation of breast cancer diagnostic biomarkers.

Introduction Circulating non-coding RNA is an ideal source to discover novel biomarkers for non-invasive screening. However, studies for the discovery of universal miRNAs in serum and exosomes for breast cancer early diagnosis are limited. Methods Based on bioinformatic analysis, in vitro and in vivo studies were performed to understand the role of identified hsa-miR-423-5p in cancer proliferation, migration, cancer stem cell properties. Next, global non-coding RNA expression profiles in blood serum and exosome were performed. hsa-miR-423-5p expression from a total of 356 peripheral blood samples was evaluated and the association of hsa-miR-423-5p expression with clinical characteristics, sensitivity and specificity for breast cancer diagnosis were assessed. Results The expression of serum and exosomal hsa-miR-423-5p is abnormally increased in breast cancer. Suppression of hsa-miR-423-5p inhibited cell proliferation and invasion in both T47D and MDA-MB-231 breast cancer cell lines, and tumor growth in vivo. Compared with 113 healthy women, quantification analysis of hsa-miR-423-5p in 224 breast cancer samples confirmed the abnormal expression. Serum hsa-miR-423-5p was significantly associated with the clinical stage (P=0.001) and Ki-67 level (P=0.004). Conclusions A translational bioinformatics analysis procedure and validation by in vitro, in vivo, and clinical samples reveal that hsa-miR-423-5p could be used as a non-invasive breast cancer biomarker.