TY - JOUR
T1 - Elevated levels of circulating osteopontin are associated with a poor survival after resection of cholangiocarcinoma
AU - Loosen, Sven H.
AU - Roderburg, Christoph
AU - Kauertz, Katja L.
AU - Pombeiro, Ines
AU - Leyh, Catherine
AU - Benz, Fabian
AU - Vucur, Mihael
AU - Longerich, Thomas
AU - Koch, Alexander
AU - Braunschweig, Till
AU - Ulmer, Tom F.
AU - Heidenhain, Christoph
AU - Tacke, Frank
AU - Binneboesel, Marcel
AU - Schmeding, Maximilian
AU - Trautwein, Christian
AU - Neumann, Ulf P.
AU - Luedde, Tom
PY - 2017/10
Y1 - 2017/10
N2 - Background & Aims: Cholangiocarcinoma (CCA) represents a primary hepatic malignancy with incidence and mortality rising globally. Surgical treatment has remained the only potentially curative treatment option, but it is still unclear which patients benefit most from extended liver surgery, highlighting the need for new pre-operative stratification strategies. Osteopontin is a secreted extracellular glyco-phosphoprotein that has been associated with inflammation, metabolic disorders and cancer. Here, we examined the potential of circulating osteopontin serum levels as a diagnostic or prognostic biomarker in patients with CCA undergoing extended liver surgery.Methods: Osteopontin expression levels were analysed in human and murine CCA tumour samples, using semi-quantitative reverse transcriptase PCR and immunohistochemistry. Osteopontin serum concentrations were measured by enzyme-linked immunosorbent assay in 107 patients with CCA undergoing elective tumour resection as well as 55 healthy controls. Results were correlated with clinical data.Results: Correlating with an upregulation in CCA tumour cells and the tumour stroma, serum levels of osteopontin were elevated in patients with cholangiocarcinoma compared to healthy controls and patients with primary sclerosing cholangitis. Importantly, pre-and postoperative elevations of osteopontin showed a striking association with poor postoperative survival.Conclusions: Serum osteopontin concentrations represent a promising prognostic biomarker in patients resectable CCA which could help to guide preoperative treatment decisions and to identify patients that will particularly benefit from extended liver surgery.Lay summary: Extended liver surgery is the only potentially curative treatment for patients with cholangiocarcinoma (CCA/biliary cancer), but it is currently unclear which patients benefit most from surgery. Detecting serum levels of osteopontin - a specific secreted glycoprotein involved in multiple human diseases - in CCA patients might help to identify those patients that particularly benefit from tumour resection. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
AB - Background & Aims: Cholangiocarcinoma (CCA) represents a primary hepatic malignancy with incidence and mortality rising globally. Surgical treatment has remained the only potentially curative treatment option, but it is still unclear which patients benefit most from extended liver surgery, highlighting the need for new pre-operative stratification strategies. Osteopontin is a secreted extracellular glyco-phosphoprotein that has been associated with inflammation, metabolic disorders and cancer. Here, we examined the potential of circulating osteopontin serum levels as a diagnostic or prognostic biomarker in patients with CCA undergoing extended liver surgery.Methods: Osteopontin expression levels were analysed in human and murine CCA tumour samples, using semi-quantitative reverse transcriptase PCR and immunohistochemistry. Osteopontin serum concentrations were measured by enzyme-linked immunosorbent assay in 107 patients with CCA undergoing elective tumour resection as well as 55 healthy controls. Results were correlated with clinical data.Results: Correlating with an upregulation in CCA tumour cells and the tumour stroma, serum levels of osteopontin were elevated in patients with cholangiocarcinoma compared to healthy controls and patients with primary sclerosing cholangitis. Importantly, pre-and postoperative elevations of osteopontin showed a striking association with poor postoperative survival.Conclusions: Serum osteopontin concentrations represent a promising prognostic biomarker in patients resectable CCA which could help to guide preoperative treatment decisions and to identify patients that will particularly benefit from extended liver surgery.Lay summary: Extended liver surgery is the only potentially curative treatment for patients with cholangiocarcinoma (CCA/biliary cancer), but it is currently unclear which patients benefit most from surgery. Detecting serum levels of osteopontin - a specific secreted glycoprotein involved in multiple human diseases - in CCA patients might help to identify those patients that particularly benefit from tumour resection. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
KW - Cancer
KW - Biomarker
KW - Prognosis
KW - CA19-9
KW - CEA
KW - CCA
KW - Osteopontin
KW - LONG-TERM SURVIVAL
KW - INTRAHEPATIC CHOLANGIOCARCINOMA
KW - PERIHILAR CHOLANGIOCARCINOMA
KW - PANCREATIC ADENOCARCINOMA
KW - HILAR CHOLANGIOCARCINOMA
KW - PROGNOSTIC BIOMARKERS
KW - INCREASING INCIDENCE
KW - SERUM-LEVELS
KW - CANCER
KW - PROGRESSION
U2 - 10.1016/j.jhep.2017.06.020
DO - 10.1016/j.jhep.2017.06.020
M3 - Article
C2 - 28668580
SN - 0168-8278
VL - 67
SP - 749
EP - 757
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 4
ER -