Henriksen, Stine Dam

Johansen, Martin Nygård

Krarup, Henrik Bygum

Larsen, Anders Christian

Madsen, Poul Henning

Pedersen, Inge Søkilde

Stubbe, Benjamin

Thorlacius-Ussing, Ole

English

Introduction: No reliable predictive blood-based biomarkers are available for determining survival from pancreatic cancer. This combined explorative and validation study examines promoter hypermethylation of Secreted frizzled-related protein 1 (phSFRP1) in plasma-derived cell-free DNA as a predictive marker for survival and gemcitabine effectiveness in patients with stage IV pancreatic adenocarcinoma.Materials and Methods: This work consists of an explorative study and a validation study. Patients were included prospectively. Blood samples were drawn before diagnostic workup and treatment. We conducted methylation-specific polymerase chain reaction analysis of the promoter region of the SFRP1 gene, based on bisulfite treatment. Survival was analyzed with log-rank test and Cox proportional hazard regression. The adjusted model included the variables age&gt;65, WHO Performance Status, and gender.Results: The explorative study included 40 patients. Patients not receiving chemotherapy (n=15) had a mOS of 2.0 months. In gemcitabine treated patients (n=25), phSFRP1 patients had a significantly shorter median overall survival of 4.4 months compared to 11.3 months in unmethylated patients. This difference was significant in adjusted cox-regression with a HR of 4.8 (95% CI; 1.5-15.3). The validation study included 58 patients who received gemcitabine. Patients with phSFRP1 had a shorter median overall survival (3·2 months) than the unmethylated group (6.3 months). This difference was significant in adjusted cox-regression with a HR of 3.5 (95% CI; 1.8-6.7). Conlusions: In both the explorative and the validation study, phSFRP1 was associated with poorer survival in stage IV pancreatic cancer patients receiving gemcitabine treatment. This may indicate that SFRP1-positive tumors are more aggressive and less sensitive to gemcitabine treatment than tumors without SFRP1 hypermethylation. This knowledge may facilitate tailored treatment of patients with stage IV pancreatic adenocarcinoma.<br/

    Aalborg UniversitetSFRP1 Promoter Hypermethylation as a Predictor of Survival and GemcitabineEfficiency in Patients with Stage IV Pancreatic AdenocarcinomaStubbe, Benjamin; Henriksen, Stine Dam; Madsen, Poul Henning; Larsen, Anders Christian;Krarup, Henrik Bygum; Pedersen, Inge Søkilde; Johansen, Martin Nygård; Thorlacius-Ussing,OleCreative Commons LicenseCC BY 4.0Publication date:2021Document VersionPublisher's PDF, also known as Version of recordLink to publication from Aalborg UniversityCitation for published version (APA):Stubbe, B., Henriksen, S. D., Madsen, P. H., Larsen, A. C., Krarup, H. B., Pedersen, I. S., Johansen, M. N., &Thorlacius-Ussing, O. (2021). SFRP1 Promoter Hypermethylation as a Predictor of Survival and GemcitabineEfficiency in Patients with Stage IV Pancreatic Adenocarcinoma. Poster presented at DanskeKræftforskningsdage 2021, Odense, Denmark.General rightsCopyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright ownersand it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.            - Users may download and print one copy of any publication from the public portal for the purpose of private study or research.            - You may not further distribute the material or use it for any profit-making activity or commercial gain            - You may freely distribute the URL identifying the publication in the public portal -Take down policyIf you believe that this document breaches copyright please contact us at vbn@aub.aau.dk providing details, and we will remove access tothe work immediately and investigate your claim.Downloaded from vbn.aau.dk on: November 19, 2022SFRP1 Promoter Hypermethylation as a Predictor of Survival and Gemcitabine Efficiency in Patients with Stage IV Pancreatic AdenocarcinomaINTRODUCTIONPancreatic cancer is a disease with an incredibly poor prognosis. Only few prognostic and no predictive biomarkers are available.Secreted Frizzled Related Protein-1 (SFRP1) is an antagonist to the oncogenic Wnt/β-catenin pathway. SFRP1-silencing has beenlinked to poor survival in several cancers, but has not beenexamined in pancreatic cancer.AIMTo examine SFRP1 promoter hypermethylation (phSFRP1) as a prognostic marker for pancreatic cancer.METHODSWho?  Patients diagnosed with Stage IV pancreatic cancer. Patients in the discovery cohort from Aalborg university hospital, and the validation cohort from the BIOPAC study.How? Methylation specific PCRRESULTS – DISCOVERY COHORTConclusionPromoter hypermethylated SFRP1 was significantly associated with poorer survival in Gem-treated Stage IV Pancreatic Cancer Patients.Stage IV PDACn=40 (100%)mOS=3.3 monthsBest Supportive Care (BSC)n=15 (37%), mOS=2.2 monthsphSFRP1n=9, mOS=4.4 monthsGemcitabine Chemotherapy (Gem)n=25 (63%), mOS=6.2 monthsumSFRP1n=16, mOS=11.6 monthsBenjamin Emil StubbeMD, Ph.D. student, b.stubbe@rn.dkDepartment of Surgery, Aalborg University Hospital, Denmark phSFRP1n=12, mOS=2.2 monthsumSFRP1n=3, mOS=2.2 monthsStage IV PDACn=58 (100%)mOS=3.3 monthsGem, umSFRP1n=28, mOS=3.2 monthsGem, phSFRP1n=28, mOS=6.3 monthsRESULTS – VALIDATION COHORTBenjamin Emil Stubbe, MD1,5 ,Stine Dam Henriksen, MD, PhD1,2,5, Poul Henning Madsen, MSc3,5, Anders Christian Larsen, MD, PhD1,5, Henrik Bygum Krarup, MD, PhD2,3,5, Inge Søkilde Pedersen, MSc, PhD2,3,5, Martin NygårdJohansen, MSc, PhD4, Ole Thorlacius-Ussing, MD, DMcS1,2,51Department of Gastrointestinal Surgery, Aalborg University Hospital, Denmark, 2Department of Clinical Medicine, Aalborg University, Denmark,3 Department of Molecular Diagnostics, Aalborg University Hospital, Denmark, 4 Unit of Clinical Biostatistics, Aalborg University Hospital, Denmark, 5 Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark

SFRP1 Promoter Hypermethylation as a Predictor of Survival and Gemcitabine Efficiency in Patients with Stage IV Pancreatic Adenocarcinoma

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SFRP1 Promoter Hypermethylation as a Predictor of Survival and Gemcitabine Efficiency in Patients with Stage IV Pancreatic Adenocarcinoma

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