Circulating miRNAs signature on breast cancer: the MCC-Spain project

Purpose: To build models combining circulating microRNAs (miRNAs) able to identify women with breast cancer as well as different types of breast cancer, when comparing with controls without breast cancer. Method: miRNAs analysis was performed in two phases: screening phase, with a total n= 40 (10 controls and 30 BC cases) analyzed by Next Generation Sequencing, and validation phase, which included 131 controls and 269 cases. For this second phase, the miRNAs were selected combining the screening phase results and a revision of the literature. They were quantified using RT-PCR. Models were built using logistic regression with LASSO penalization. Results: The model for all cases included seven miRNAs (miR-423-3p, miR-139-5p, miR-324-5p, miR-1299, miR-101-3p, miR-186-5p and miR-29a-3p); which had an area under the ROC curve of 0.73. The model for cases diagnosed via screening only took in one miRNA (miR-101-3p); the area under the ROC curve was 0.63. The model for disease-free cases in the follow-up had five miRNAs (miR-101-3p, miR-186-5p, miR-423-3p, miR-142-3p and miR-1299) and the area under the ROC curve was 0.73. Finally, the model for cases with active disease in the follow-up contained six miRNAs (miR-101-3p, miR-423-3p, miR-139-5p, miR-1307-3p, miR-331-3p and miR-21-3p) and its area under the ROC curve was 0.82. Conclusion: We present four models involving eleven miRNAs to differentiate healthy controls from different types of BC cases. Our models scarcely overlap with those previously reported.