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. Overall design: MiRNAs derived from extracellular vesicles were isolated from serum samples of well clinically annotated breast cancer patients and control from South of Brazil