Abstract
Cholangiocarcinoma is an epithelial malignancy arising in the region between the intrahepatic bile ducts and the ampulla of Vater at the distal end of the common bile duct. The effect of current chemotherapy regimens against cholangiocarcinoma is limited, and the prognosis of patients with cholangiocarcinoma is poor. Aberrant DNA methylation and histone modification induce silencing of tumor suppressor genes and chromosomal instability during carcinogenesis. Studies have shown that the tumor suppressor genes and microRNAs (miRNAs) including MLH1, p14, p16, death-associated protein kinase (DAPK), miR-370 and miR-376c are frequently methylated in cholangiocarcinoma. Silencing of these tumor suppressor genes and miRNAs plays critical roles in the initiation and progression of cholangiocarcinoma. In addition, recent studies have demonstrated that DNA methylation inhibitors induce expression of endogenous retroviruses and exert the anti-tumor effect of via an anti-viral immune response. Aberrant DNA methylation of tumor suppressor genes and miRNAs could be a powerful biomarker for the diagnosis and treatment of cholangiocarcinoma. Epigenetic therapy with DNA methylation inhibitors holds considerable promise for the treatment of cholangiocarcinoma through the reactivation of tumor suppressor genes and miRNAs as well as the induction of an anti-viral immune response.
Highlights
Cholangiocarcinoma is an epithelial malignancy arising in the region between the intrahepatic bile ducts and the ampulla of Vater at the distal end of the common bile duct
Perihilar cholangiocarcinoma is located between the second degree bile ducts and the insertion of the cystic duct into the common bile duct, whereas distal cholangiocarcinoma is located between the origin of the cystic duct and the ampulla of Vater [1]
Several imaging modalities including computed tomography (CT) and magnetic resonance imaging (MRI) as well as serological tests including serum CA19-9 concentration are helpful for the diagnosis of cholangiocarcinoma
Summary
Cholangiocarcinoma is an epithelial malignancy arising in the region between the intrahepatic bile ducts and the ampulla of Vater at the distal end of the common bile duct. Aberrant DNA methylation and histone modification induce silencing of tumor suppressor genes and chromosomal instability, leading to the initiation and progression of various cancers [4,5,6,7]. Aberrant DNA methylation at CpG island promoters of tumor suppressor genes is frequently observed in various human malignancies including cholangiocarcinoma.
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