Roles of Hepatic Bile Acid Transporters in Hepatocellular Carcinoma

Abstract ID 98689 Poster Board 052 Objective: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy that occurs predominantly in patients with underlying chronic liver disease and cirrhosis. Sodium-taurocholate co-transporting polypeptide (NTCP) encoded by the SLC10A1 gene (solute carrier family 10 member 1) and bile salt export pump (BSEP) encoded by ABCB11 gene (ATP-binding cassette, sub-family B member 11) are two key transporters for hepatic bile acid uptake and excretion. Emerging data have implicated that the expression and function of NTCP and BSEP are altered in hepatocellular carcinoma. We aimed to systematically analyze SLC10A1 and ABCB11 expression and prognostic roles in HCC using various open databases. Methods: Expression of SLC10A1 and ABCB11 in HCC was assessed using UALCAN and GEPIA database. Correlation between SLC10A1 and ABCB11 expression and patient survival was evaluated with OncoLnc. SLC10A1 and ABCB11 genetic alterations in HCC were explored using cBioPortal. Results: Expression of SLC10A1 and ABCB11 was significantly down-regulated in the clinic-pathological characteristics (cancer stages, tumor grade, nodal metastasis status, and histological subtypes) examined in HCC patients compared to normal counterparts. Positive gene expression correlation between SLC10A1 and ABCB11 in hepatocellular carcinoma was observed. Clinically, low expression of SLC10A1 and ABCB11 was correlated with shorter overall survival in HCC patients (Logrank p-value=0.0009 vs p-value = 0.02). Among HCC cases with SLC10A1 and ABCB11 genetic alterations, mutations were the most common type of alteration (data from TCGA Liver Hepatocellular Carcinoma, PanCancer Atlas). Conclusion: These observations indicate that SLC10A1 and ABCB11 may function as a potential tumor suppressor gene. In HCC patients, SLC10A1 and ABCB11 expression levels may serve as prognostic predictive markers.