Small extracellular vesicle-encapsulated miR-181b-5p, miR-222-3p and let-7a-5p: Next generation plasma biopsy-based diagnostic biomarkers for inflammatory breast cancer

Abstract

Inflammatory breast cancer (IBC) is a rare, but aggressive entity of breast carcinoma with rapid dermal lymphatic invasion in young females. It is either poorly or misdiagnosed as mastitis because of the absence of a distinct lump. Small extracellular vesicles (sEVs) circulating in liquid biopsies are a novel class of minimally invasive diagnostic alternative to invasive tissue biopsies. They modulate cancer progression via shuttling their encapsulated cargo including microRNAs (miRNAs) into recipient cells to either trigger signaling or induce malignant transformation of targeted cells. Plasma sEVs < 200 nm were isolated using a modified cost-effective polyethylene glycol (PEG)-based precipitation method and compared to standard methods, namely ultracentrifugation and a commercial kit, where the successful isolation was verified by different approaches. We evaluated the expression levels of selected sEV-derived miR-181b-5p, miR-222-3p and let-7a-5p using quantitative real PCR (qPCR). Relative to non-IBC, our qPCR data showed that sEV-derived miR-181b-5p and miR-222-3p were significantly upregulated, whereas let-7a-5p was downregulated in IBC patients. Interestingly, receiver operating characteristic (ROC) curves analysis revealed that diagnostic accuracy of let-7a-5p alone was the highest for IBC with an area under curve (AUC) value of 0.9188, and when combined with miR-222-3p the AUC was improved to 0.973. Further, 38 hub genes were identified using bioinformatics analysis. Together, circulating sEV-derived miR-181b-5p, miR-222-3p and let-7a-5p serve as promising non-invasive diagnostic biomarkers for IBC.

miRNAs in the Era of Personalized Medicine: From Biomarkers to Therapeutics

“…For instance, deregulation of miR-200b, miR-200c, miR-205, and miR-487 has been observed in lung cancer [ 12 ], supporting the concept that smoking-related epigenetic changes might be considered as putative biomarkers for lung diseases. Moreover, the development of novel cost-effective extracellular vesicle-based liquid biopsy techniques aid miRNA-based diagnostics, as recently demonstrated for inflammatory breast cancer [ 28 ].…”

The Biology and Function of Extracellular Vesicles in Cancer Development

“…Previous reports have indicated that EVs containing anti-tumor drugs can induce cell apoptosis in HCCs (Slomka et al, 2020). Furthermore, EVs containing miRNA mimics such as let-7a have been found to induce cell apoptosis in breast cancer (Ahmed et al, 2021). In addition, EVs have the ability to regulate autophagy.…”

Anti-Cancer Role and Therapeutic Potential of Extracellular Vesicles

“…MiR-150-3p has been suggested as a prognostic biomarker for HCC [ 97 ]. MicroRNAs are important diagnostic biomarkers for breast cancer [ 212 , 213 ]. It is important to identify not only miRNAs but also lncRNAs for diagnosis [ 214 ].…”