Universität zu Köln

Loosen, Sven H., Tacke, Frank, Puthe, Niklas, Binneboesel, Marcel, Wiltberger, Georg, Alizai, Patrick H., Kather, Jakob N., Paffenholz, Pia, Ritz, Thomas, Koch, Alexander, Bergmann, Frank, Trautwein, Christian, Longerich, Thomas, Roderburg, Christoph, Neumann, Ulf P. and Luedde, Tom (2019). High baseline soluble urokinase plasminogen activator receptor (suPAR) serum levels indicate adverse outcome after resection of pancreatic adenocarcinoma. Carcinogenesis, 40 (8). S. 947 - 956. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2180

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Abstract

Surgical resection represents the only potentially curative therapy for patients with pancreatic adenocarcinoma (PDAC), an aggressive malignancy with a very limited 5-year survival rate. However, even after complete tumor resection, many patients are still facing an unfavorable prognosis underlining the need for better preoperative stratification algorithms. Here, we explored the role of the secreted glycoprotein soluble urokinase plasminogen activator receptor (suPAR) as a novel circulating biomarker for patients undergoing resection of PDAC. Serum levels of suPAR were measured by enzyme-linked immunosorbent assay (ELISA) in an exploratory as well as a validation cohort comprising a total of 127 PDAC patients and 75 healthy controls. Correlating with a cytoplasmic immunohistochemical expression of uPAR in PDAC tumor cells, serum levels of suPAR were significantly elevated in PDAC patients compared to healthy controls and patient with PDAC precursor lesions. Importantly, patients with high preoperative suPAR levels above a calculated cutoff value of 5.956 ng/ml showed a significantly reduced overall survival after tumor resection. The prognostic role of suPAR was further corroborated by uni- and multivariate Cox-regression analyses including parameters of systemic inflammation, liver and kidney function as well as clinico-pathological patients' characteristics. Moreover, high baseline suPAR levels identified those patients particularly susceptible to acute kidney injury and surgical complications after surgery. In conclusion, our data suggest that circulating suPAR represents a novel prognostic marker in PDAC patients undergoing tumor resection that might be a useful addition to existing preoperative stratification algorithms for identifying patients that particularly benefit from extended tumor resection.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Loosen, Sven H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tacke, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Puthe, Niklas UNSPECIFIED UNSPECIFIED UNSPECIFIED Binneboesel, Marcel UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiltberger, Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Alizai, Patrick H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kather, Jakob N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Paffenholz, Pia UNSPECIFIED UNSPECIFIED UNSPECIFIED Ritz, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Bergmann, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Trautwein, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Longerich, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Roderburg, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Neumann, Ulf P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Luedde, Tom UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-144963
DOI:	10.1093/carcin/bgz033
Journal or Publication Title:	Carcinogenesis
Volume:	40
Number:	8
Page Range:	S. 947 - 956
Date:	2019
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2180
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CANCER; CELLS; UPAR; GEMCITABINE; SUPPRESSION; EXPRESSION; MORTALITY; DIAGNOSIS; GROWTH Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14496