Serum microRNA microarray analysis identifies miR-4429 and miR-4689 are potential diagnostic biomarkers for biliary atresia

Abstract

This study aimed to investigate pathogenesis and novel diagnostic biomarkers of biliary atresia (BA). Serum samples from infants with BA and non-BA neonatal cholestasis (NC) were collected for miRNA microarray analysis, and then differentially expressed miRNAs were screened. Differentially expressed miRNAs were validated by qRT-PCR using an independent serum samples from infants with BA and NC. Diagnostic utility of validated miRNAs was further analyzed using serum samples by receiver-operating characteristic curve analysis. Totally, 13 differentially expressed miRNAs were identified including 11 down-regulated and 2 up-regulated ones. Target genes of hsa-miR-4429 and hsa-miR-4689 were significantly involved in FoxO signaling pathway. Eight differentially expressed miRNAs were chosen for validation by qRT-PCR analysis, and four miRNAs (hsa-miR-150-3p, hsa-miR-4429, hsa-miR-4689 and hsa-miR-92a-3p) were differentially expressed. The area under the curve of hsa-miR-4429 and hsa-miR-4689 was 0.789 (sensitivity = 83.33%, specificity = 80.00%) and 0.722 (sensitivity = 66.67%, specificity = 80.00%), respectively. Differentially expressed miRNAs including hsa-miR-4429 and hsa-miR-4689 might play critical roles in BA by regulating their target genes, and these two miRNAs may have the potential to become diagnostic biomarkers.