Transporter Expression in Noncancerous and Cancerous Liver Tissue from Donors with Hepatocellular Carcinoma and Chronic Hepatitis C Infection Quantified by LC-MS/MS Proteomics
Transporter Expression in Noncancerous and Cancerous Liver Tissue from Donors with Hepatocellular Carcinoma and Chronic Hepatitis C Infection Quantified by LC-MS/MS Proteomics
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DOI：
10.1124/dmd.117.077289
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发表时间：
2018-02-01
影响因子：
3.9
通讯作者：
Unadkat, Jashvant D.
中科院分区：
文献类型：
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作者：
Billington, Sarah;Ray, Adrian S.;Unadkat, Jashvant D.
采用LC-MS/MS蛋白质组学方法，对慢性丙型肝炎合并肝细胞癌（HCV-HCC）患者的癌（C, n = 8）及邻近非癌（NC, n = 33）肝组织中主要肝胆药物转运蛋白（NTCP、OATPs、OCT1、BSEP、BCRP、MATE1、MRPs、P-gp）的蛋白表达进行定量分析。在此，我们将我们的结果与之前来自非感染、非肝硬化（对照组，n = 36）和丙型肝炎肝硬化（n = 30）肝脏的数据进行了比较。与对照肝脏相比，NC和C型HCV-HCC组织的膜蛋白产量分别下降了31%和67%。与对照肝脏相比，除了NTCP、MRP2和MATE1外，转运蛋白表达在NC（38%-76%）和C (56%-96%) HCV-HCC组织中下降。在NC型HCV-HCC组织中，NTCP表达增加（113%），MATE1表达减少（58%），MRP2表达相对于对照肝脏不变。在HCV-HCC组织中，与对照肝脏相比，NTCP和MRP2表达下降（63%,56%），MATE1表达不变。与hcv -肝硬化肝脏相比，除了NTCP、OCT1、BSEP和MRP2外，转运蛋白在NC（41%-71%）和C (54%-89%) HCV-HCC组织中的表达降低。在NC型HCV-HCC组织中，NTCP和MRP2表达增加（362%,142%），而OCT1和BSEP表达不变。在HCV-HCC组织中，OCT1和BSEP的表达相对于hcv -肝硬化肝脏降低（90%,80%），而NTCP和MRP2的表达不变。与匹配的NC组织相比，ooatp2b1、BSEP、MRP2和MRP3在C型HCV-HCC组织中的表达降低（56%-72%）（n = 8），但其他转运蛋白的表达不变。这些数据将有助于未来预测HCV-HCC患者转运蛋白介导的肝细胞药物浓度。
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.