LncRNA-mRNA coexpression analysis reveals distinct pathogenic mechanisms for subtypes of congenital biliary dilatation.

BACKGROUND/PURPOSE: Congenital biliary dilatation (CBD) is a bile duct malformation often associated with pancreaticobiliary maljunction. Different subtypes of CBD have been noted for clinical differences, but their pathogenic mechanisms are unclear.

METHODS: To elucidate the genetic basis of CBD, we performed lncRNA and mRNA sequencing and bioinformatic analysis on 18 cystic and 18 fusiform CBD samples.

RESULTS: We identified differentially expressed mRNAs and lncRNAs between the two types of CBD, and constructed coexpression modules that correlated with clinical characteristics of CBD using weighted gene coexpression network analysis. We found that the brown module was the highest positive correlation with fusiform CBD (R = 0.67, p = 7.9e-6) and contained the most genes. We then built a lncRNA-mRNA coexpression network to identify potential target genes of lncRNAs in CBD, and a protein-protein interaction network to investigate the hub genes from the target genes and the brown module. Finally, we performed enrichment analyses and found differences between cystic and fusiform CBD in hepatobiliary system development, liver and pancreas development involving hub genes ONECUT1 and HNF1B that could be regulated by corresponding lncRNAs.

CONCLUSION: Our study suggests that lncRNAs may modulate pancreaticobiliary duct development differently in cystic and fusiform CBD, providing new insights for etiology studies and clinical treatment.