Abstract
Soluble urokinase-type plasminogen activator receptor, suPAR, as a prognostic biomarker in advanced pancreatic cancer.
Author
person
Rikke Løvendahl Eefsen
Department of Oncology, Experimental Cancer Therapy Unit, Herlev, Denmark
info_outline
Rikke Løvendahl Eefsen, Ib Jarle Christensen, Dan Calatyud, Astrid Zedlitz Johansen, Inna Markovna Chen, Louise Skau Rasmussen, Per Pfeiffer, Niels Henrik Hollander, Fahimeh Andersen, Julia S. Johansen, Gunilla Hoyer-Hansen
Full text
Authors
person
Rikke Løvendahl Eefsen
Department of Oncology, Experimental Cancer Therapy Unit, Herlev, Denmark
info_outline
Rikke Løvendahl Eefsen, Ib Jarle Christensen, Dan Calatyud, Astrid Zedlitz Johansen, Inna Markovna Chen, Louise Skau Rasmussen, Per Pfeiffer, Niels Henrik Hollander, Fahimeh Andersen, Julia S. Johansen, Gunilla Hoyer-Hansen
Organizations
Department of Oncology, Experimental Cancer Therapy Unit, Herlev, Denmark, Department of Pathology, Copenhagen University Hospital, Herlev Gentofte Hospital, Herlev, Denmark, Herlev Gentofte Hospital, Herlev, Copenhagen, Denmark, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Herlev, Denmark, Aalborg University Hospital, Aalborg, Denmark, Odense University Hospital, Odense, Denmark, Zealand University Hospital, Naestved, Denmark, Hilleroed Hospital, Hillerød, Denmark, The Finsen Laboratory, BRIC, Copenhagen, Denmark
Abstract Disclosures
Research Funding
Other
Different fundings in Denmark
Background:
High levels of intact and cleaved forms of the urokinase-type Plasminogen Activator Receptor (uPAR) in tissue and blood are associated with a poor prognosis in several types of cancer, including lung, colon, bladder, and cholangiocarcinoma. The soluble forms of uPAR (suPAR) have not been investigated in patients with pancreatic ductal adenocarcinoma (PDAC). The aim was to determine if circulating levels of intact and cleaved suPAR were associated with overall survival (OS) in patients with advanced PDAC.
Methods:
Patients with PDAC stage 3 or 4 were consecutively included in the BIOPAC study (ClinicalTrials.gov ID: NCT03311776) in a training cohort (n = 230, age 45-89 years, 56% females) from Herlev Hospital and a validation cohort (n = 115, age 40-82 years, 59% females) from four other Danish hospitals between 2008 to 2014. A total of 95% of the patients in the training cohort and 93% in the validation cohort received first-line palliative chemotherapy. One patient was alive at the time of analysis at 8 years follow-up. Serum samples were collected prior to palliative chemotherapy. Different suPAR forms were determined using time-resolved fluorescence immunoassays (TR-FIA). The Cox proportional hazards model was used for uni- and multivariate analyses. Age, performance status, stage (4 vs 3), gender, Charlson age-adjusted comorbidity index, and CA19-9 were included in the multivariate analysis for OS.
Results:
In the training cohort, high level of suPAR domain I was an independent biomarker of short OS (HR, 1.37, 95% CI 1.15-1.63, p = 0.0004). High CA19-9 (HR, 1.08, 95% CI 1.04-1.12, p < 0.0001), PS, and stage were also independent prognostic parameters in the training cohort. In the validation cohort, high level of suPAR domain I (HR, 1.91, 95% CI 1.36-2.69, p = 0.0002) and CA 19-9 (HR, 1.09, 95% CI 1.01-1.17, p = 0.02) were confirmed as independent prognostic biomarkers for short OS. No correlation was observed between suPAR domain 1 and CA19-9 (r = 0.059, p = 0.21).
Conclusions:
A high pretreatment circulating level of suPAR domain I is associated with a short OS in patients with advanced PDAC, and the biomarker is independent of CA19-9. The results warrant further investigation of suPAR domain 1 as a biomarker in patients with PDAC.
Clinical status
Clinical
12 organizations
2 drugs
2 targets
Organization
Department of Oncology and Haematology, Division of Oncology, University Hospital of Modena, Modena, ItalyOrganization
Experimental Cancer Therapy UnitOrganization
Copenhagen University HospitalOrganization
Herlev Gentofte HospitalOrganization
Aalborg University HospitalOrganization
Odense University HospitalOrganization
Zealand University HospitalOrganization
Hilleroed HospitalOrganization
The Finsen LaboratoryOrganization
BRICDrug
CA19-9Drug
suPARTarget
suPARTarget
CA19-9