Imaging, Diagnosis, Prognosis Identification of Circulating MicroRNA Signatures for Breast Cancer Detection

Purpose: There is a quest for novel noninvasive diagnosticmarkers for the detection of breast cancer. The goal of this study is to identify circulating microRNA (miRNA) signatures using a cohort of Asian Chinese patients with breast cancer, and to compare miRNA profiles between tumor and serum samples. Experimental Design: miRNA from paired breast cancer tumors, normal tissue, and serum samples derived from 32 patients were comprehensively profiled using microarrays or locked nucleic acid real-time PCRpanels. Serum samples fromhealthy individuals (n1⁄4 22)were also used as normal controls. Significant serummiRNAs, identifiedby logistic regression,were validated in an independent set of serumsamples from patients (n 1⁄4 132) and healthy controls (n 1⁄4 101). Results: The 20 most significant miRNAs differentially expressed in breast cancer tumors included miRNA (miR)-21, miR-10b, and miR-145, previously shown to be dysregulated in breast cancer. Only 7 miRNAs were overexpressed in both tumors and serum, suggesting that miRNAs may be released into the serum selectively. Interestingly, 16 of the 20 most significant miRNAs differentially expressed in serum samples were novel. MiR-1, miR-92a, miR-133a, and miR-133b were identified as the most important diagnostic markers, and were successfully validated; receiver operating characteristic curves derived from combinations of these miRNAs exhibited areas under the curves of 0.90 to 0.91. Conclusion: The clinical use of miRNA signatures as a noninvasive diagnostic strategy is promising, but shouldbe further validated for different subtypes of breast cancers.ClinCancer Res; 19(16); 4477–87. 2013