Identification of miRNAs enriched in Extracellular vesicles derived from serum samples of breast cancer patients

Purpose: In this study, we performed RNA-seq analysis as a screening strategy to identify EV-miRNAs derived from serum of well clinically annotated breast cancer (BC) patients from South of Brazil. Methods: EVs from three groups of samples, healthy controls (CT), luminal A (LA), and triple negative (TNBC), were isolated from serum using a precipitation method and analyzed by RNA-seq (screening phase). Subsequently, four EV-miRNAs (miR-142-5p, miR-150-5p, miR-320a, and miR-4433b-5p) were selected to be quantified by RT-qPCR in individual samples (test phase). Results: A panel composed of miR-142-5p, miR-320a, and miR-4433b-5p discriminated BC patients from CT with an AUC of 0.8387 (93.33% sensitivity, 68.75% specificity). In addition, the combination of miR-142-5p and miR-320a, presented an AUC of 0.941 (100% sensitivity, 93.80% specificity) in distinguishing LA patients from CT. Interestingly, decrease expression of miR-142-5p and miR-150-5p were significantly associated with more advanced tumor grades (grade III), while the decrease expression of miR-142-5p and miR-320a with larger tumor size. Conclusion: These results provide insights into the potential application of EVs-miRNAs from serum as novel specific markers for early diagnosis of BC. MiRNAs derived from extracellular vesicles were isolated from serum samples of well clinically annotated breast cancer patients and control from South of Brazil