title: Downregulation of organic cation transporter 1 (SLC22A1) is associated with tumor progression and reduced patient survival in human cholangiocellular carcinoma.
abstract: Cholangiocellular carcinoma (CCA) is a primary hepatic malignancy derived from cholangiocytes. The prognosis for CCA patients is very poor and conventional chemotherapy has been proven ineffective in improving long‑term patient survival rates. Organic cation transporters (OCTs) mediate the transport of a broad spectrum of endogenous substrates and the detoxification of xenobiotics. Moreover, OCTs are considered responsible for the responsiveness towards platinum‑based chemotherapies. Currently, there are no data available regarding the role of OCTs in CCA. Therefore, the aim of this study was to investigate the expression of OCT1 and OCT3 in CCA and the corresponding non-neoplastic tumor‑surrounding tissue (TST). OCT1 (SLC22A1) and OCT3 (SLC22A3) mRNA expression was measured in primary human CCA by real-time PCR (n=27). Protein expression was determined by western blot analysis and immunohistochemistry. Data were correlated with the clinicopathological parameters of CCA. Real-time PCR demonstrated a downregulation of the expression of SLC22A1 and SLC22A3 in CCA, compared to that in TST (p<0.001). A low SLC22A1 expression was associated with a worse patient survival (p<0.05). The downregulation of SLC22A1 was significantly associated with advanced CCA stages, since tumors with a low SLC22A1 mRNA expression presented with larger tumor diameters (p=0.02). There were no significant differences in tumor characteristics or patient survival in relation to the level of SLC22A3 expression. Western blot analysis and immunohistochemistry confirmed the downregulation of OCT1 and OCT3 protein levels in cancerous tissue compared to those in TST. In conclusion, the downregulation of OCT1 is associated with tumor progression and worse overall patient survival rates.
authors: Department of Hepatobiliary and Transplantation Surgery, Johannes Gutenberg University Mainz, Mainz, Germany.
authors: Anja
authors: A
authors: Lautem
authors: Michael
authors: M
authors: Heise
authors: Andreas
authors: A
authors: Gräsel
authors: Maria
authors: M
authors: Hoppe-Lotichius
authors: Nina
authors: N
authors: Weiler
authors: Daniel
authors: D
authors: Foltys
authors: Johanna
authors: J
authors: Knapstein
authors: Jörn M
authors: JM
authors: Schattenberg
authors: Arno
authors: A
authors: Schad
authors: Anca
authors: A
authors: Zimmermann
authors: Gerd
authors: G
authors: Otto
authors: Hauke
authors: H
authors: Lang
authors: Peter R
authors: PR
authors: Galle
authors: Marcus
authors: M
authors: Schuchmann
authors: Tim
authors: T
authors: Zimmermann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000401:mortality; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000401:mortality; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D027702:Organic Cation Transporter 1 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000099254:Organic Cation Transporter 3
chemical_list: D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; D012333:RNA, Messenger; D000099254:Organic Cation Transporter 3