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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Sven H. Loosen - , Rheinisch-Westfälische Technische Hochschule Aachen (Autor:in)
  • Annemarie Breuer - , Rheinisch-Westfälische Technische Hochschule Aachen (Autor:in)
  • Frank Tacke - , Rheinisch-Westfälische Technische Hochschule Aachen, Charité – Universitätsmedizin Berlin (Autor:in)
  • Jakob N. Kather - , Rheinisch-Westfälische Technische Hochschule Aachen (Autor:in)
  • Joao Gorgulho - , Rheinisch-Westfälische Technische Hochschule Aachen (Autor:in)
  • Patrick H. Alizai - , Rheinisch-Westfälische Technische Hochschule Aachen (Autor:in)
  • Jan Bednarsch - , Rheinisch-Westfälische Technische Hochschule Aachen (Autor:in)
  • Anjali A. Roeth - , Rheinisch-Westfälische Technische Hochschule Aachen (Autor:in)
  • Georg Lurje - , Rheinisch-Westfälische Technische Hochschule Aachen (Autor:in)
  • Sophia M. Schmitz - , Rheinisch-Westfälische Technische Hochschule Aachen (Autor:in)
  • Jonathan F. Brozat - , Rheinisch-Westfälische Technische Hochschule Aachen (Autor:in)
  • Pia Paffenholz - , Universität zu Köln (Autor:in)
  • Mihael Vucur - , Rheinisch-Westfälische Technische Hochschule Aachen (Autor:in)
  • Thomas Ritz - , Universität Heidelberg (Autor:in)
  • Alexander Koch - , Rheinisch-Westfälische Technische Hochschule Aachen (Autor:in)
  • Christian Trautwein - , Rheinisch-Westfälische Technische Hochschule Aachen (Autor:in)
  • Tom F. Ulmer - , Rheinisch-Westfälische Technische Hochschule Aachen (Autor:in)
  • Christoph Roderburg - , Rheinisch-Westfälische Technische Hochschule Aachen, Charité – Universitätsmedizin Berlin (Autor:in)
  • Thomas Longerich - , Universität Heidelberg (Autor:in)
  • Ulf P. Neumann - , Rheinisch-Westfälische Technische Hochschule Aachen (Autor:in)
  • Tom Luedde - , Rheinisch-Westfälische Technische Hochschule Aachen (Autor:in)

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

OriginalspracheEnglisch
Aufsatznummer100080
FachzeitschriftJHEP Reports
Jahrgang2
Ausgabenummer2
PublikationsstatusVeröffentlicht - Apr. 2020
Peer-Review-StatusJa
Extern publiziertJa

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

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