Serum MicroRNAs as Potential Biomarkers of Primary Biliary Cirrhosis

BACKGROUND Circulating microRNAs (miRNAs), which are extremely stable and protected from RNAse-mediated degradation in body fluids, have emerged as candidate biomarkers for many diseases. The present study aimed to identify a serum microRNA (miRNA) expression profile that could serve as a novel diagnostic biomarker for primary biliary cirrhosis (PBC). METHODS Serum miRNA expression was investigated using four cohorts comprising 380 participants (healthy controls and patients with PBC) recruited between August 2010 and June 2013. miRNA expression was initially analyzed by Illumina sequencing using serum samples pooled from 3 patients and 3 controls. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was then used to evaluate the expression of selected miRNAs in a screening set (n = 40). A logistic regression model was then constructed using a training cohort (n = 192) and validated using another cohort (n = 142). The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. RESULTS We identified a miRNA panel (hsa-miR-122-5p, hsa-miR-141-3p, and hsa-miR-26b-5p) with a high diagnostic accuracy for PBC (AUC = 0.905, 95% confidence interval (CI) = 0.857 to 0.953; sensitivity = 80.5%, specificity = 88.3%). There was a significant difference between AUC values of the miRNA panel and those of alkaline phosphatase (ALP) (AUC = 0.537, difference between areas = 0.314, 95% CI = 0.195 to 0.434, P<0.001), and those of antinuclear antibody (ANA) (AUC = 0.739, difference between areas = 0.112, 95% CI = 0.012 to 0.213, P = 0.0282). CONCLUSION We identified a serum microRNA panel with considerable clinical value in PBC diagnosis. The results indicate that the miRNA panel is a more sensitive and specific biomarker for PBC than ALP and ANA.