SFRP1 Promoter Hypermethylation as a Predictor of Survival and Gemcitabine Efficiency in Patients with Stage IV Pancreatic Adenocarcinoma
| Autor: | Benjamin Emil Stubbe, Stine Dam Henriksen, Poul Henning Madsen, Anders Christian Larsen, Henrik Krarup, Inge Søkilde Pedersen, Martin Nygaard Johansen, Ole Thorlacius-Ussing |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | 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 Gemcitabine Efficiency in Patients with Stage IV Pancreatic Adenocarcinoma ', Danske Kræftforskningsdage 2021, Odense, Denmark, 26/08/2021-27/08/2021 . Aalborg University |
| Popis: | 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>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. |
| Databáze: | OpenAIRE |
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