Circulating miRNAs revealed as surrogate molecular signatures for the early detection of breast cancer.

The miRNAs have well studied roles in cancer. Here, we identified altered miRNA expression by global miRNA profiling in peripheral blood mononuclear cells (PBMCs) of breast cancer (n = 15) and healthy subjects (n = 15), and further validated the selected miRNAs in PBMCs (n = 45), blood plasma (n = 45) and breast tissue samples (n = 09). The expression of altered miRNAs was also evaluated in PBMCs among early stage (n = 32), advanced stage (n = 13), triple positive (n = 5) and triple negative (n = 5) breast cancer patients. Results showed differential pattern of expressions of these miRNAs in multiple cohorts, however in early stage breast cancer, miR-106a-5p and miR-454-3p were upregulated (p < 0.05), miR-195-5p and miR-495 were downregulated (p < 0.05) in PBMCs. In addition, these miRNAs were also significantly associated with cancer and ErbB signaling pathways. Multiple regression analysis and receiver-operative curve (ROC) analysis of miR-195-5p and miR-495 with area under curve (AUC) of 0.901 showed best discriminating combination for early stage breast cancer detection. In summary, the present study delineated the importance of miR-195-5p and miR-495 miRNAs as prospective circulating surrogate molecular signatures for early detection of breast cancer.

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