Transporter expression in non-cancerous and cancerous liver tissue from donors with hepatocellular carcinoma and chronic hepatitis C infection quantified by LC-MS/MS proteomics.

Protein expression of major hepatobiliary drug transporters (NTCP, OATPs, OCT1, BSEP, BCRP, MATE1, MRPs and P-gp) in cancerous (C, n=8) and adjacent non-cancerous (NC, n=33) liver tissues obtained from chronic hepatitis C patients with hepatocellular carcinoma (HCV-HCC) were quantified by LC-MS/MS proteomics. Herein, we compare our results with our previous data from non-infected non-cirrhotic (control, n=36) and HCV-cirrhotic (n=30) livers. The amount of membrane protein yielded from NC and C HCV-HCC tissues decreased (31%, 67%) relative to control livers. In comparison to control livers, with the exception of NTCP, MRP2 and MATE1, transporter expression decreased in NC (38-76%) and C (56-96%) HCV-HCC tissues. In NC HCV-HCC tissues NTCP expression increased (113%), MATE1 expression decreased (58%) and MRP2 expression was unchanged relative to control livers. In C HCV-HCC tissues, NTCP and MRP2 expression decreased (63%, 56%) and MATE1 expression was unchanged relative to control livers. Compared to HCV-cirrhotic livers, aside from NTCP, OCT1, BSEP and MRP2, transporter expression decreased in NC (41-71%) and C (54-89%) HCV-HCC tissues. In NC HCV-HCC tissues, NTCP and MRP2 expression increased (362%, 142%), whilst OCT1 and BSEP expression were unchanged. In C HCV-HCC tissues, OCT1 and BSEP expression decreased (90%, 80%) relative to HCV-cirrhotic livers, while NTCP and MRP2 expression were unchanged. Expression of OATP2B1, BSEP, MRP2 and MRP3 decreased (56-72%) in C HCV-HCC tissues in comparison to matched NC tissues (n=8) but the expression of other transporters was unchanged. These data will helpful in future to predict transporter-mediated hepatocellular drug concentrations in patients with HCV-HCC.