title: Organic Cation Transporter 1 (OCT1) mRNA expression in hepatocellular carcinoma as a biomarker for sorafenib treatment.
abstract: BACKGROUND
  The polyspecific organ cation transporter 1 (OCT1) is one of the most important active influx pumps for drugs like the kinase inhibitor sorafenib. The aim of this retrospective study was the definition of the role of intratumoral OCT1 mRNA expression in hepatocellular carcinoma (HCC) as a biomarker in systemic treatment with sorafenib.
  
  
  METHODS
  OCT1 mRNA expression levels were determined in biopsies from 60 primary human HCC by real time PCR. The data was retrospectively correlated with clinical parameters.
  
  
  RESULTS
  Intratumoral OCT1 mRNA expression is a significant positive prognostic factor for patients treated with sorafenib according to Cox regression analysis (HR 0.653, 95%-CI 0.430-0.992; p = 0.046). Under treatment with sorafenib, a survival benefit could be shown using the lower quartile of intratumoral OCT1 expression as a cut-off. Macrovascular invasion (MVI) was slightly more frequent in patients with low OCT1 mRNA expression (p = 0.037). Treatment-induced AFP response was not associated with intratumoral OCT1 mRNA expression levels (p = 0.633).
  
  
  CONCLUSIONS
  This study indicates a promising role for intratumoral OCT1 mRNA expression as a prognostic biomarker in therapeutic algorithms in HCC. Further prospective studies are warranted on this topic.
authors.affiliation: 1st Department of Medicine, University Medical Center Mainz, Langenbeckstr. 1, Mainz, 55131, Germany. daniel.grimm@unimedizin-mainz.de.
authors.forename: Daniel
authors.initials: D
authors.lastname: Grimm
authors.affiliation: 1st Department of Medicine, University Medical Center Mainz, Langenbeckstr. 1, Mainz, 55131, Germany. jlieb@students.uni-mainz.de.
authors.forename: Jonas
authors.initials: J
authors.lastname: Lieb
authors.affiliation: University Medical Center Mainz, Institute of Medical Biostatistics, Epidemiology and Informatics, Obere Zahlbacher Str. 69, Mainz, 55131, Germany. weyer@uni-mainz.de.
authors.forename: Veronika
authors.initials: V
authors.lastname: Weyer
authors.affiliation: 1st Department of Medicine, University Medical Center Mainz, Langenbeckstr. 1, Mainz, 55131, Germany. johanna.knapstein@unimedizin-mainz.de.
authors.forename: Johanna
authors.initials: J
authors.lastname: Vollmar
authors.affiliation: 1st Department of Medicine, University Medical Center Mainz, Langenbeckstr. 1, Mainz, 55131, Germany. felix.darstein@unimedizin-mainz.de.
authors.forename: Felix
authors.initials: F
authors.lastname: Darstein
authors.affiliation: Department of General-, Visceral- and Transplantation Surgery, University Medical Center Mainz, Langenbeckstr. 1, Mainz, 55131, Germany. anja.lautem@unimedizin-mainz.de.
authors.forename: Anja
authors.initials: A
authors.lastname: Lautem
authors.affiliation: Department of General-, Visceral- and Transplantation Surgery, University Medical Center Mainz, Langenbeckstr. 1, Mainz, 55131, Germany. maria.hoppe-lotichius@unimedizin-mainz.de.
authors.forename: Maria
authors.initials: M
authors.lastname: Hoppe-Lotichius
authors.affiliation: 1st Department of Medicine, University Medical Center Mainz, Langenbeckstr. 1, Mainz, 55131, Germany. sandra.koch@unimedizin-mainz.de.
authors.forename: Sandra
authors.initials: S
authors.lastname: Koch
authors.affiliation: Department of Pathology, University Medical Center Mainz, Langenbeckstr. 1, Mainz, 55131, Germany. arno.schad@unimedizin-mainz.de.
authors.forename: Arno
authors.initials: A
authors.lastname: Schad
authors.affiliation: 1st Department of Medicine, University Medical Center Mainz, Langenbeckstr. 1, Mainz, 55131, Germany. joern.schattenberg@unimedizin-mainz.de.
authors.forename: Jörn M
authors.initials: JM
authors.lastname: Schattenberg
authors.affiliation: 1st Department of Medicine, University Medical Center Mainz, Langenbeckstr. 1, Mainz, 55131, Germany. marcus-alexander.woerns@unimedizin-mainz.de.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Wörns
authors.affiliation: 1st Department of Medicine, University Medical Center Mainz, Langenbeckstr. 1, Mainz, 55131, Germany. arndt.weinmann@unimedizin-mainz.de.
authors.forename: Arndt
authors.initials: A
authors.lastname: Weinmann
authors.affiliation: 1st Department of Medicine, University Medical Center Mainz, Langenbeckstr. 1, Mainz, 55131, Germany. peter.galle@unimedizin-mainz.de.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
authors.affiliation: 1st Department of Medicine, University Medical Center Mainz, Langenbeckstr. 1, Mainz, 55131, Germany. tim.zimmermann@unimedizin-mainz.de.
authors.forename: Tim
authors.initials: T
authors.lastname: Zimmermann
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D027682:Cation Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D027702:Organic Cation Transporter 1 / Q000096:biosynthesis* / Q000235:genetics; D010671:Phenylurea Compounds / Q000008:administration & dosage; D012333:RNA, Messenger / Q000096:biosynthesis; D000077157:Sorafenib
chemical_list: D014408:Biomarkers, Tumor; D027682:Cation Transport Proteins; D027702:Organic Cation Transporter 1; D010671:Phenylurea Compounds; D012333:RNA, Messenger; D009536:Niacinamide; D000077157:Sorafenib