The Study Of Circulating MicroRNAs Of MiR-106a?363 Clusters On X Chromosome As A New Diagnostic Marker For Breast Cancer

Novel non-invasive biomarkers with high sensitivity and specificity for diagnosis of early breast cancer(BC)are urgently needed in clinic at present.Recent studies have revealed that miRNAs could be stable and easily detectable in serum or plasma and have the potential use as biomarkers for diagnosis,prognosis and classification of diseases in various cancers including BC.We conducted a three-phase study to identify circulating miRNAs from the miR-106a?363 cluster on chromosome X for detecting BC based on qRT-PCR.The identified miRNAs were further evaluated in tissue samples of BC as well as exosomes isolated from plasma and serum separately.In addition,the potential relationship between the identified miRNAs and clinicopathological features of BC was analyzed.Up-regulated levels of four plasma miRNAs(miR-106a-3p,miR-106a-5p,miR-20b-5p and miR-92a-2-5p)and four serum miRNAs(miR-106a-5p,miR-19b-3p,miR-20b-5p and miR-92a-3p)in BC were identified and validated,which can discriminate BC patients from HCs.Two overlapping miRNAs(miR-106a-5p and miR-20b-5p)were consistently up-regulated in BC tissues.Expression patterns of exosomal miRNAs were concordant with those in plasma and serum except plasma-derived exosomal miR-20b-5p,which indicated the potential use of exosomal miRNAs as biomarkers.The relationship between the identified miRNAs and clinical parameters(TNM stage,histological grade,ER and HER2 status)was analyzed.All the identified plasma miRNAs were found to be elevated and showed significantly different expression in patients with grade ?+? compared to those with grade ?.Higher expression levels of miR-106a-5p and miR-20b-5p were found in patients with HER2-negative status in comparison to patients with HER2-positive status.However,no significant difference was observed between the serum miRNAs and BC patients' characteristics.None of the identified miRNAs was significantly associated with clinical TNM stage.We identified the plasma four-miRNA panel and serum four-miRNA panel from miR-106a?363 cluster as novel promising biomarkers for diagnosis of BC.