• miRNA Biomarkers, Plasma Extracellular Vesicles, and Breast Cancer Detection
  • Mahdiye Feizi Elyasabad,1,* Hadi Maleki-Kakelar,2 Morteza Taheri-Anganeh,3
    1. Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
    2. Solid Tumor Research Center, Cellular and Molecular Medicine Institute Urmia University of Medical Sciences
    3. Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran


  • Introduction: Mammography screening has improved early breast cancer detection, lowering death and advanced breast cancer rates. Extracellular vesicles (EVs), such as exosomes and microvesicles, allow cancer cells to communicate with one another during the disease's progression. The purpose of this work is to uncover biomarkers in multiplexed extracellular vesicle liquid biopsies that may reliably categorize lesions identified by mammography.
  • Methods: We studied plasma from 95 prospectively recruited participants with breast lesions, including 65 with benign lesions and 30 with malignant ones. None of the invasive carcinomas metastasized. We isolated HER2 and CD24-expressing extracellular vesicles (EVs) from each plasma sample using track-etched magnetic nanopore technology, then assessed their miRNA concentration using next-generation sequencing. We evaluated the effectiveness of EV-miRNA biomarkers in predicting malignancy and used LASSO classification to generate a panel of four complementary EV-miRNA biomarkers, which we verified using qPCR.
  • Results: We found 11 differently enriched miRNAs in HER2+ EVs and 6 in CD24+ EVs from women with malignant lesions vs those with benign lesions. Some miRNAs have AUCs of up to 0.77, such as miR-330 from HER2+ EVs, and 0.65 for miR-213 from EVs. LASSO classification chose a panel of four EV miRNAs—miR-140, miR-468, miR-15b, and miR-121—for breast cancer categorization.
  • Conclusion: This work suggests that lipids in blood plasma EVs might be useful indicators for breast cancer diagnosis. The HER2+ and CD24+ EV subpopulations include complementary biomarkers that can be validated in larger studies and reliably predict early-stage breast cancer in women with breast lesions.
  • Keywords: Breast Cancer, Extracellular Vesicles, Biomarkers, miRNA, HER2