Novel MicroRNA biomarkers revealed in the serum and bile of thioacetamide induced cholangiocarcinoma.

Cholangiocarcinoma is often very challenging to diagnose due to high false negative biopsy rates. There are known precursors to cholangiocarcinoma such as primary sclerosing cholangitis and hepatitis; however, identifying early and sensitive biomarkers for liver injury and tumor progression could enhance cancer diagnosis, prognosis, and management. Recent studies have suggested blood and bile-based microRNA (miRNA) panels performed better than existing tumor markers. To further investigate this, we conducted next-generation sequencing of thioacetamide (TAA) induced cholangiocarcinoma in an established rat model. We identified 2938 unique differentially expressed genes (DEGs) and 27 differentially expressed miRNAs (DEMs) between tumor bearing rats and normal controls. Pathway analyses on the DEGs and DEMs revealed the molecular mechanisms of hepatic hyperplasia and nephritis. To filter for ideal biomarkers, we further performed qPCR on bile and serum. Three miRNAs (miR-146b-5p, miR-223-3p and miR-214-3p) overlapped with the DEMs from solid tumors. Therefore, those miRNAs have the potential to serve as early and sensitive biomarkers for TAA-induced cholangiocarcinoma. Notably, no previous study has demonstrated the role of miR-146-5p on cancer development.