Circulating levels of soluble urokinase plasminogen activator receptor predict outcome after resection of biliary tract cancer

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Sven H. Loosen - , RWTH Aachen University (Author)
  • Annemarie Breuer - , RWTH Aachen University (Author)
  • Frank Tacke - , RWTH Aachen University, Charité – Universitätsmedizin Berlin (Author)
  • Jakob N. Kather - , RWTH Aachen University (Author)
  • Joao Gorgulho - , RWTH Aachen University (Author)
  • Patrick H. Alizai - , RWTH Aachen University (Author)
  • Jan Bednarsch - , RWTH Aachen University (Author)
  • Anjali A. Roeth - , RWTH Aachen University (Author)
  • Georg Lurje - , RWTH Aachen University (Author)
  • Sophia M. Schmitz - , RWTH Aachen University (Author)
  • Jonathan F. Brozat - , RWTH Aachen University (Author)
  • Pia Paffenholz - , University of Cologne (Author)
  • Mihael Vucur - , RWTH Aachen University (Author)
  • Thomas Ritz - , Heidelberg University  (Author)
  • Alexander Koch - , RWTH Aachen University (Author)
  • Christian Trautwein - , RWTH Aachen University (Author)
  • Tom F. Ulmer - , RWTH Aachen University (Author)
  • Christoph Roderburg - , RWTH Aachen University, Charité – Universitätsmedizin Berlin (Author)
  • Thomas Longerich - , Heidelberg University  (Author)
  • Ulf P. Neumann - , RWTH Aachen University (Author)
  • Tom Luedde - , RWTH Aachen University (Author)

Abstract

Background & Aims: Surgical resection is the only potentially curative therapy for patients with biliary tract cancer (BTC), but 5-year survival rates after tumor resection have remained below 30%, corroborating the need for better stratification tools to identify the ideal surgical candidates. The soluble urokinase plasminogen activator receptor (suPAR) represents a mediator of inflammation and has been associated with distinct types of cancer. In this study, we evaluated a potential role of suPAR as a novel biomarker in patients undergoing BTC resection. Methods: Tumor expression of uPAR was analyzed by immunohistochemistry in 108 BTC samples. Serum levels of suPAR were analyzed by ELISA in a training and validation cohort comprising a total of 117 patients with BTC and 76 healthy controls. Results: High tumoral uPAR expression was associated with an adverse outcome after BTC resection. Accordingly, circulating levels of suPAR were significantly elevated in patients with BTC compared to healthy controls, as well as in patients with primary sclerosing cholangitis. Using a small training set, we established an optimal prognostic suPAR cut-off value of 3.72 ng/ml for patients with BTC. Importantly, preoperative suPAR serum levels above this cut-off value were associated with significantly impaired overall survival in both the training and validation cohort. Multivariate Cox-regression analysis including various clinicopathological parameters such as tumor stage, markers of inflammation and organ dysfunction, as well as tumor markers, revealed circulating suPAR levels as an independent prognostic marker following BTC resection. Finally, high preoperative suPAR levels were indicative of acute kidney injury after tumor resection. Conclusion: Circulating suPAR represents a previously unrecognized biomarker in patients with resectable BTC, which might help to preoperatively identify the ideal candidates for liver surgery. Lay summary: Surgical resection represents the only curative treatment option for patients with biliary tract cancer, but not all patients benefit to the same extent in terms of overall survival. Here, we provide evidence that serum levels of an inflammatory mediator (suPAR) are indicative of a patient's postoperative outcome and might thus help to identify the ideal surgical candidates.

Details

Original languageEnglish
Article number100080
JournalJHEP Reports
Volume2
Issue number2
Publication statusPublished - Apr 2020
Peer-reviewedYes
Externally publishedYes

Keywords

Sustainable Development Goals

Keywords

  • acute kidney injury, biomarker, BTC, CA19-9, CCA, CEA, cholangiocarcinoma, suPAR