Integrated Tissue and Blood miRNA Expression Profiles Identify Novel Biomarkers for Accurate Non-Invasive Diagnosis of Breast Cancer: Preliminary Results and Future Clinical Implications.

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We aimed to identify miRNAs that were closely related to breast cancer (BRCA). By integrating several methods including significance analysis of microarrays, fold change, Pearson's correlation analysis, t test, and receiver operating characteristic analysis, we developed a decision-tree-based scoring algorithm, called Optimized Scoring Mechanism for Primary Synergy MicroRNAs (O-PSM). Five synergy miRNAs (hsa-miR-139-5p, hsa-miR-331-3p, hsa-miR-342-5p, hsa-miR-486-5p, and hsa-miR-654-3p) were identified using O-PSM, which were used to distinguish normal samples from pathological ones, and showed good results in blood data and in multiple sets of tissue data. These five miRNAs showed accurate categorization efficiency in BRCA typing and staging and had better categorization efficiency than experimentally verified miRNAs. In the Protein-Protein Interaction (PPI) network, the target genes of hsa-miR-342-5p have the most regulatory relationships, which regulate carcinogenesis proliferation and metastasis by regulating Glycosaminoglycan biosynthesis and the Rap1 signaling pathway. Moreover, hsa-miR-342-5p showed potential clinical application in survival analysis. We also used O-PSM to generate an R package uploaded on github (SuFei-lab/OPSM accessed on 22 October 2021). We believe that miRNAs included in O-PSM could have clinical implications for diagnosis, prognostic stratification and treatment of BRCA, proposing potential significant biomarkers that could be utilized to design personalized treatment plans in BRCA patients in the future.