Expression of lncRNAs in children with pancreaticobiliary maljunction: functional analysis and potential biomarkers.

Abstract

Pancreaticobiliary maljunction (PBM) leads to higher rates of complications, including cholangitis, pancreatitis, and malignancies. The aim of the present study was to investigate the expression profile of long non-coding RNAs (lncRNAs) and their potential role as biomarkers in children with pancreaticobiliary maljunction. The differential expression of lncRNAs and messenger RNA (mRNAs) from pediatric patients with pancreaticobiliary maljunction and control subjects was analyzed using a commercial microarray and later validated with qRT-PCR. The potential biological functions of differentially expressed genes were explored based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. The ability of potential lncRNA biomarkers to predict pancreaticobiliary maljunction was assessed based on the area under the receiver operating characteristic curve (AUC). There were 2915 mRNAs and 173 lncRNAs upregulated, and 2121 mRNAs and 316 lncRNAs downregulated in PBM cases compared to controls. The enriched Gene Ontology categories associated with differentially expressed mRNAs were extracellular matrix, extracellular region, and kinetochore. The most enriched Kyoto Encyclopedia pathway was protein digestion and absorption, which was associated with cancer and PI3K-Akt signaling. Analysis of cis- and trans-target genes predicted that a single lncRNA was able to regulate several mRNAs. The qRT-PCR results for NR_110876, NR_132344, XR_946886, and XR_002956345 were consistent with the microarray results, and the difference was statistically significant for NR_132344, XR_946886, and XR_002956345 (p < 0.05). AUC was significant only for XR_946886 (0.837, p < 0.001). Our results implicate lncRNAs in common bile duct pathogenesis in PBM, and they identify XR_946886 as a potential biomarker for the disease.