Circulating Mi Rnas From The MiR?188 Cluster On Chromosome X As Novel Diagnostic Biomarkers For BC

Background: Numerous studies have revealed that circulating mi RNAs have great potential of being non-invasive biomarkers for various cancers,including breast cancer(BC).The aim of this study was to explore the expression patterns of mi RNAs from the mi R-188 cluster in the blood circulation of BC patients and try to discover novel circulating signatures for the early diagnosis of BC.Methods: A total of 400 plasma samples(from 200 BC patients and 200 healthy controls(HCs))and 406 serum samples(from 204 BC patients and 202 HCs)were collected and analyzed in a three-phase study.Expression levels of mi RNAs in the mi R-188 cluster were detected by quantitative reverse transcription polymerase chain reaction(q RT? PCR).The identified mi RNAs were further analyzed in plasma and serum exosomes(from 32 BC patients and 32 HCs),36 breast tumor tissues and the matched 36 normal tissues.Results: Three plasma mi RNAs(mi R-188-3p,mi R-500a-5p and mi R-501-5p)and five serum mi RNAs(mi R-188-3p,mi R-501-3p,mi R-502-3p,mi R-532-3p and mi R-532-5p)were found to be significantly up-regulated in BC patients compared with HCs(P value<0.05).Expression levels of mi R-188-3p presented a statistical trend of positive correlation between plasma and serum samples.We then constructed a three-mi RNA plasma panel and a five-mi RNA serum panel.For the plasma panel,the areas under the curves(AUCs)of receiver operating characteristic(ROC)were 0.882 for the training phase,0.650 for the testing phase and 0.805 for the external validation phase,while for the serum panel,the AUCs were 0.788,0.837 and 0.895 for the three phases respectively.Among all the identified mi RNAs,only mi R-501-5p was found to be relatively up-regulated in BC tissue compared with HCs.In exosomes samples of BC,all the identified mi RNAs were significantly up-regulated,except plasma-derived mi R-501-5p and serum-derived mi R-532-3p and mi R-532-5p.Conclusion: In this study,we identified three plasma mi RNAs and five serum mi RNAs from the mi R-188 cluster which could serve as promising non-invasive biomarkers for BC diagnosis.