Pathogenesis of Choledochal Cyst: Insights from Genomics and Transcriptomics

Abstract

Choledochal cysts (CC) is characterized by extra- and/or intra-hepatic b\ile duct dilations. There are two main theories, “pancreaticobiliary maljunction” and “congenital stenosis of bile ducts” proposed for the pathogenesis of CC. Although family cases or CC associated with other anomalies have been reported, the molecular pathogenesis of CC is still poorly understood. Recent advances in transcriptomics and genomics analysis platforms have unveiled key expression signatures/genes/signaling pathways in the pathogenesis of human diseases including CC. This review summarizes insights from genomics and transcriptomics studies into the pathogenesis of CC, with the aim to improve (i) our understanding of its underlying complex pathomechanisms, and (ii) clinical management of different subtypes of CC, in particular their associated hepatic fibrotic change and their risk of malignancy transformation.

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

“…More importantly, familial cases have been previously reported, including mother–daughter, father–daughter, and identical twin sisters. Despite previous reports of associated genetic variants and chromosomal abnormalities, selecting mutated genes and validating them in animal experiments remains challenging due to the multigenetic nature of CBD and the limited number of cases 8,17 . Therefore, sequencing through different modalities and analyzing more cases can help to gain insight into the complex molecular pathogenesis of the disease.…”

“…Some surgeons have suggested that congenital biliary dilatation may consist of two disease entities, cystic and fusiform types, due to the different pathologies and operative strategies of each group 5 . Although such clinical differences have been noted, the corresponding differences in pathogenesis and molecular markers remain unclear 8,9 …”

“…5 Although such clinical differences have been noted, the corresponding differences in pathogenesis and molecular markers remain unclear. 8,9 Long noncoding RNAs (lncRNAs) are often longer than 200 nucleotides in length and can account for up to 80% of noncoding RNA. 10 They participate in diverse biological processes including gene transcription as well as RNA translation, shearing and degradation.…”

Non-cirrhotic portal hypertension secondary to cholangiointestinal anastomotic stricture after choledochal cyst excision: a case report

“…Further, CYP7B1 is involved in the metabolism of bile acids, and loss of activity is associated with liver failure in children ( 20 ). Furthermore, Ye et al ( 21 ) reported several known genetic loci with unique functions in the development and progression of choledochal cysts and suggested that they may be caused by the combined action of multiple polymorphic genes that act independently or cooperatively. However, an association between mutations in the CYP7B1 locus and choledochal cysts has not been reported, and the relationship between them requires further exploration.…”

Experience of surgical management of rare cases of choledochal cyst in last five years—tertiary care reflection

“…Caroli disease, commonly known as type V CC, is an autosomal recessive condition thought to be caused by ductal plate embryological distortion (11). Caroli disease is linked to biliary atresia because the pathophysiology of ductal plate deformity is similar, but it is also linked to autosomal recessive polycystic kidney disease (PKD) and, less commonly, autosomal dominant PKD (12).…”