%0 Journal Article
%T Downregulation of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) in human hepatocellular carcinoma and their prognostic significance
%A Michael Heise
%A Anja Lautem
%A Johanna Knapstein
%A J£¿rn M Schattenberg
%A Maria Hoppe-Lotichius
%A Daniel Foltys
%A Nina Weiler
%A Anca Zimmermann
%A Arno Schad
%A Dirk Gr¨¹ndemann
%A Gerd Otto
%A Peter R Galle
%A Marcus Schuchmann
%A Tim Zimmermann
%J BMC Cancer
%D 2012
%I BioMed Central
%R 10.1186/1471-2407-12-109
%X OCT1 (SLC22A1) and OCT3 (SLC22A3) mRNA expression was measured in primary human HCC and corresponding non neoplastic tumor surrounding tissue (TST) by real time PCR (n = 53). Protein expression was determined by western blot analysis and immunofluorescence. Data were correlated with the clinicopathological parameters of HCCs.Real time PCR showed a downregulation of SLC22A1 and SLC22A3 in HCC compared to TST (p ¡Ü 0.001). A low SLC22A1 expression was associated with a worse patient survival (p < 0.05). Downregulation was significantly associated with advanced HCC stages, indicated by a higher number of T3 tumors (p = 0.025) with a larger tumor diameter (p = 0.035), a worse differentiation (p = 0.001) and higher AFP-levels (p = 0.019). In accordance, SLC22A1 was less frequently downregulated in tumors with lower stages who underwent transarterial chemoembolization (p < 0.001) and liver transplantation (p = 0.001). Tumors with a low SLC22A1 expression (< median) showed a higher SLC22A3 expression compared to HCC with high SLC22A1 expression (p < 0.001). However, there was no significant difference in tumor characteristics according to the level of the SLC22A3 expression.In the western blot analysis we found a different protein expression pattern in tumor samples with a more diffuse staining in the immunofluorescence suggesting that especially OCT1 is not functional in advanced HCC.The downregulation of OCT1 is associated with tumor progression and a worse patient survival.Hepatocellular carcinoma (HCC) is one of the most common human malignancies worldwide with growing numbers of patients frequently leading to death [1]. In the majority of cases tumors grow multifocal and show a high rate of recurrence with a poor prognosis [2]. In general, HCCs do not respond to classical chemotherapeutics. Treatment options, especially with regard to a systemic therapy, are very limited. Therefore, new markers and therapeutic usable targets are urgently needed.Transporters contribute
%K OCT1
%K OCT3
%K SLC22A1
%K SLC22A3
%K Hepatocellular carcinoma
%K HCC
%U http://www.biomedcentral.com/1471-2407/12/109