Sven H Loosen1, Christoph Roderburg1, Katja L Kauertz2, Inês Pombeiro2, Catherine Leyh2, Fabian Benz2, Mihael Vucur2, Thomas Longerich3, Alexander Koch1, Till Braunschweig3, Tom F Ulmer4, Christoph Heidenhain4, Frank Tacke1, Marcel Binnebösel4, Maximilian Schmeding5, Christian Trautwein1, Ulf P Neumann4, Tom Luedde6. 1. Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany. 2. Division of Gastroenterology, Hepatology and Hepatobiliary Oncology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany. 3. Institute of Pathology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany. 4. Department of Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany. 5. Department of Surgery, Klinikum Dortmund, Beurhausstraße 40, 44137 Dortmund, Germany. 6. Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany; Division of Gastroenterology, Hepatology and Hepatobiliary Oncology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany. Electronic address: tluedde@ukaachen.de.
Abstract
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.
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 murineCCA 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.
Authors: Jesus M Banales; Jose J G Marin; Angela Lamarca; Pedro M Rodrigues; Shahid A Khan; Lewis R Roberts; Vincenzo Cardinale; Guido Carpino; Jesper B Andersen; Chiara Braconi; Diego F Calvisi; Maria J Perugorria; Luca Fabris; Luke Boulter; Rocio I R Macias; Eugenio Gaudio; Domenico Alvaro; Sergio A Gradilone; Mario Strazzabosco; Marco Marzioni; Cédric Coulouarn; Laura Fouassier; Chiara Raggi; Pietro Invernizzi; Joachim C Mertens; Anja Moncsek; Sumera Rizvi; Julie Heimbach; Bas Groot Koerkamp; Jordi Bruix; Alejandro Forner; John Bridgewater; Juan W Valle; Gregory J Gores Journal: Nat Rev Gastroenterol Hepatol Date: 2020-06-30 Impact factor: 46.802
Authors: Sven H Loosen; Maximilian Schulze-Hagen; Tobias Püngel; Lukas Bündgens; Theresa Wirtz; Jakob N Kather; Mihael Vucur; Pia Paffenholz; Münevver Demir; Philipp Bruners; Christiane Kuhl; Christian Trautwein; Frank Tacke; Tom Luedde; Alexander Koch; Christoph Roderburg Journal: Crit Care Explor Date: 2020-08-05
Authors: Mark Luedde; Sanchari Roy; Hans-Joerg Hippe; David Vargas Cardenas; Martina Spehlmann; Mihael Vucur; Pia Hoening; Sven Loosen; Norbert Frey; Christian Trautwein; Tom Luedde; Alexander Koch; Frank Tacke; Christoph Roderburg Journal: Sci Rep Date: 2018-06-27 Impact factor: 4.379
Authors: Christoph Roderburg; Sven H Loosen; Jan Bednarsch; Patrick H Alizai; Anjali A Roeth; Sophia M Schmitz; Mihael Vucur; Mark Luedde; Pia Paffenholz; Frank Tacke; Christian Trautwein; Tom F Ulmer; Ulf Peter Neumann; Tom Luedde Journal: Int J Mol Sci Date: 2021-06-18 Impact factor: 5.923
Authors: Ines Pombeiro; Sven H Loosen; Sanchari Roy; Florian Schueller; Lukas Niewenhuisen; Mark Luedde; Mihael Vucur; Frank Tacke; Marcel Binnebösel; Wenzel Schoening; Christian Trautwein; Tom Luedde; Ulf Peter Neumann; Christoph Roderburg Journal: J Clin Med Date: 2018-07-13 Impact factor: 4.241