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.
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 a...
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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2021-01-01
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Series: | PLoS ONE |
Online Access: | https://doi.org/10.1371/journal.pone.0250642 |
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author | Sarah Hamdy Ahmed Nancy A Espinoza-Sánchez Ahmed El-Damen Sarah Atef Fahim Mohamed A Badawy Burkhard Greve Mohamed El-Shinawi Martin Götte Sherif Abdelaziz Ibrahim |
author_facet | Sarah Hamdy Ahmed Nancy A Espinoza-Sánchez Ahmed El-Damen Sarah Atef Fahim Mohamed A Badawy Burkhard Greve Mohamed El-Shinawi Martin Götte Sherif Abdelaziz Ibrahim |
author_sort | Sarah Hamdy Ahmed |
collection | DOAJ |
description | 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. |
first_indexed | 2024-12-21T02:09:59Z |
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institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-21T02:09:59Z |
publishDate | 2021-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
spelling | doaj.art-bd41449e62f2464c8c5438ffce85854a2022-12-21T19:19:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01164e025064210.1371/journal.pone.0250642Small extracellular vesicle-encapsulated miR-181b-5p, miR-222-3p and let-7a-5p: Next generation plasma biopsy-based diagnostic biomarkers for inflammatory breast cancer.Sarah Hamdy AhmedNancy A Espinoza-SánchezAhmed El-DamenSarah Atef FahimMohamed A BadawyBurkhard GreveMohamed El-ShinawiMartin GötteSherif Abdelaziz IbrahimInflammatory 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.https://doi.org/10.1371/journal.pone.0250642 |
spellingShingle | Sarah Hamdy Ahmed Nancy A Espinoza-Sánchez Ahmed El-Damen Sarah Atef Fahim Mohamed A Badawy Burkhard Greve Mohamed El-Shinawi Martin Götte Sherif Abdelaziz Ibrahim 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. PLoS ONE |
title | 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. |
title_full | 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. |
title_fullStr | 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. |
title_full_unstemmed | 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. |
title_short | 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. |
title_sort | 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 |
url | https://doi.org/10.1371/journal.pone.0250642 |
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