PT  - JOURNAL ARTICLE
AU  - Billington, Sarah
AU  - Ray, Adrian S.
AU  - Salphati, Laurent
AU  - Xiao, Guangqing
AU  - Chu, Xiaoyan
AU  - Humphreys, W. Griffith
AU  - Liao, Mingxiang
AU  - Lee, Caroline A.
AU  - Mathias, Anita
AU  - Hop, Cornelis E. C. A.
AU  - Rowbottom, Christopher
AU  - Evers, Raymond
AU  - Lai, Yurong
AU  - Kelly, Edward J.
AU  - Prasad, Bhagwat
AU  - Unadkat, Jashvant D.
TI  - Transporter Expression in Noncancerous and Cancerous Liver Tissue from Donors with Hepatocellular Carcinoma and Chronic Hepatitis C Infection Quantified by LC-MS/MS Proteomics
AID  - 10.1124/dmd.117.077289
DP  - 2018 Feb 01
TA  - Drug Metabolism and Disposition
PG  - 189--196
VI  - 46
IP  - 2
4099  - http://dmd.aspetjournals.org/content/46/2/189.short
4100  - http://dmd.aspetjournals.org/content/46/2/189.full
SO  - Drug Metab Dispos2018 Feb 01; 46
AB  - Protein expression of major hepatobiliary drug transporters (NTCP, OATPs, OCT1, BSEP, BCRP, MATE1, MRPs, and P-gp) in cancerous (C, n = 8) and adjacent noncancerous (NC, n = 33) liver tissues obtained from patients with chronic hepatitis C with hepatocellular carcinoma (HCV-HCC) were quantified by LC-MS/MS proteomics. Herein, we compare our results with our previous data from noninfected, noncirrhotic (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 with 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 with 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%), whereas OCT1 and BSEP expression was unchanged. In C HCV-HCC tissues, OCT1 and BSEP expression decreased (90%, 80%) relative to HCV-cirrhotic livers, whereas NTCP and MRP2 expression was unchanged. Expression of OATP2B1, BSEP, MRP2, and MRP3 decreased (56%–72%) in C HCV-HCC tissues in comparison with matched NC tissues (n = 8), but the expression of other transporters was unchanged. These data will be helpful in the future to predict transporter-mediated hepatocellular drug concentrations in patients with HCV-HCC.