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

Research output: Contribution to conference without publisher/journalPosterResearch

9 Downloads (Pure)

Abstract

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.
Original languageEnglish
Publication date26 Aug 2021
Publication statusPublished - 26 Aug 2021
EventDanske Kræftforskningsdage 2021 - Odeon Konferencecenter, Odense, Denmark
Duration: 26 Aug 202127 Aug 2021
https://www.dccc.dk/kalender/Afholdte-arrangementer/danske-kraftforskningsdage-2021

Conference

ConferenceDanske Kræftforskningsdage 2021
LocationOdeon Konferencecenter
Country/TerritoryDenmark
CityOdense
Period26/08/202127/08/2021
Internet address

Keywords

  • biomarker
  • cancer
  • pancreatic cancer
  • prognostic
  • survival
  • blood-based
  • epigenetics
  • personalized therapy
  • DNA Methylation

Fingerprint

Dive into the research topics of 'SFRP1 Promoter Hypermethylation as a Predictor of Survival and Gemcitabine Efficiency in Patients with Stage IV Pancreatic Adenocarcinoma'. Together they form a unique fingerprint.

Cite this