The promising role of epigenetic mediators and microRNAs in the early diagnosis of cholangiocarcinoma (Review)

Abstract

Cholangiocarcinoma (CC) is a highly lethal malignant tumor which arises from the biliary tract epithelium and is notoriously difficult to diagnose. Common risk factors for CC are primary sclerosing cholangitis, liver fluke infestation and hepatolithiasis. Although CCs are relatively uncommon tumors, the worldwide rising incidences and mortality rate for intrahepatic CC (ICC) renders it a disease of interest for research. CCs are usually fatal due to the typically late clinical presentation and the lack of effective non-surgical therapeutic modalities. The overall survival rate, including following tumor resection, is poor with <5% of patients surviving 5 years and this rate has not significantly improved over the past 30 years. Thus, there is a need to diagnose CC at an early stage, and advances in immunohistochemistry, molecular genetics, pharmacogenomics and personalized medicine may aid in the study of the pathological basis of CC at the gene and protein level. Understanding the genetic and proteomic alterations in CC would not only increase the therapeutic efficacy, but would also provide a better treatment strategy. Epigenetic alterations that induce gene expression in cancers have been well established. Among the epigenetic mechanisms, targeting DNA hypermethylation and histone deacetylation with DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors has been reported in a number of cancer types. In CC, targeting the epigenetic pathways appears to be a promising approach for treatment. This review aims to provide a comprehensive overview of the putative role of epigenetic alterations and proteomic alterations in CC. Furthermore, the role of these alterations in early diagnosis, as prognostic markers, and therapeutics for better treatment strategies will be highlighted. Contents 1. Introduction 2. Diagnostic snags 3. Mechanism of tumorigenesis 4. Epigenetic alterations in cholangiocarcinoma 5. Diagnostic development 6. Epigenetic therapy of cancer 7. Conclusions