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.
CONCLUSIONS: 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.
方法:为了阐明CBD的遗传基础,我们对18个囊性和18个梭形CBD样本进行了lncRNA和mRNA测序和生物信息学分析。
结果:我们鉴定了两种类型的CBD之间差异表达的mRNA和lncRNA,并利用加权基因共表达网络分析构建了与CBD临床特征相关的共表达模块。我们发现棕色模块与梭形CBD的正相关性最高(R=0.67,p=7.9e-6),并且包含最多的基因。然后,我们建立了一个lncRNA-mRNA共表达网络,以鉴定CBD中lncRNA的潜在靶基因,和蛋白质-蛋白质相互作用网络,以研究目标基因和棕色模块的hub基因。最后,我们进行了富集分析,发现囊性和梭形CBD在肝胆系统发育中的差异,肝脏和胰腺发育涉及hub基因ONECUT1和HNF1B,可由相应的lncRNAs调节。
结论:我们的研究表明,lncRNAs可能在囊性和梭形CBD中不同地调节胰胆管发育,为病因学研究和临床治疗提供新的见解。