Background. Inflammatory Breast Cancer (IBC) is a rare, but aggressive subtype of breast carcinoma with dermal lymphatic invasion in young females. IBC is poorly diagnosed as it develops vast rapidly relative to other non-IBC and without distinct lumps formation, moreover, it is usually misdiagnosed with mastitis. Nanosized exosomes (20-200nm) circulating in liquid biopsies are a promising minimally invasive diagnostic alternative to standard biopsies. In cancer microenvironment, they modulate cancer progression via shuttling their encapsulated microRNAs (miRNAs) into recipient cells to either trigger signaling or induce malignant transformation of targeted cells. While small non-coding regulatory miRNAs are an already known cancer biomarkers, exosomal miRNAs serve as a novel class of diagnostic biomarkers. The present study aims to evaluate the expression levels of exosomal miRNAs relevant to IBC pathogenesis. Design/Materials/Methods. This is a prospective case-control study that includes 77 females; 57 were diagnosed with breast cancer (34 non-IBC and 23 IBC), while 20 were healthy volunteers. All have signed an informed consent to be enrolled in this investigation. Patients included were neither pregnant nor issued with bloodborne or autoimmune disease, while healthy subjects had no oncologic history. Plasma circulating exosomes were isolated using precipitation and ultracentrifugation methods. The successful isolation was verified by dynamic light scattering (DLS), transmission electron microscopy (TEM), Western blot (WB), and Dot blot (DB). The expression level of exosomes-derived miR-181b-5p, miR-222-5p and let-7a was quantified by qPCR. Afterwards, that expression level was verified in the human non-IBC MDA-MB-231 and IBC SUM149 cell lines. Statistics. Difference between groups was tested using Student’s t-test through IBM SPSS statistics software package, version 24. A p < 0.05 was considered significant. Results. DLS and TEM analysis revealed that nanovesicles with 146.65 nm were successfully isolated. Moreover, CD63, HSP70, Alix90 and GM130 antibodies used in DB and WB have further confirmed the successful isolation. Relative to non-IBC, our qPCR showed that plasma exosomes-derived miR-181b-5p and miR-222-5p were significantly (p <0.0001 and p <0.01, respectively) upregulated in IBC, whereas exosomal let-7a was significantly (p <0.0001) downregulated in IBC. Further, the expression levels of miR181-5p and miR-222 were upregulated in SUM-149-derived exosomes relative to those of MDA-MB-231-derived exosomes ( Both p < 0.001), while the expression levels of let-7a did not significantly change. Diagnostic accuracy of the candidate plasma exosomal miRNAs was assessed via receiver operating characteristic (ROC) curves analysis. Interestingly, Area Under Curve (AUC) was 0.826 for miR-181-5p (p <0.0001), 0.7212 for miR-222-5p (p <0.0001), and 0.9188 for let7a (p <0.01). Additionally, bioinformatical analysis for predicted targets of the identified exosomal miRNAs will be assessed. Conclusion. Exosomes derived miR-181-5p, miR-222-5p and let7-7a may act as non-invasive diagnostic biomarkers to discriminate IBC from non-IBC patients.

Citation Format: Sarah Hamdy Ahmed, Ahmed El-Damen, Mohamed A. Badawy, Mohamed El-Shinawi, Martin Götte, Sherif Abdelaziz Ibrahim. Plasma exosomal miRNAs: A minimally invasive diagnostic biomarker for inflammatory breast carcinoma [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS19-07.