Validation of SFRP1 Promoter Hypermethylation in Plasma as a Prognostic Marker for Survival and Gemcitabine Effectiveness in Patients with Stage IV Pancreatic Adenocarcinoma

No reliable predictive blood-based biomarkers are available for determining survival from pancreatic adenocarcinoma (PDAC). This combined discovery and validation study examines promoter hypermethylation (ph) of secreted frizzled-related protein 1 (SFRP1) in plasma-derived cell-free DNA as an indepe...

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Bibliographic Details
Published in:Cancers 2021-11, Vol.13 (22), p.5717
Main Authors: Stubbe, Benjamin Emil, Henriksen, Stine Dam, Madsen, Poul Henning, Larsen, Anders Christian, Krarup, Henrik Bygum, Pedersen, Inge Søkilde, Johansen, Martin Nygård, Thorlacius-Ussing, Ole
Format: Article
Language:English
Subjects:
Adenocarcinoma
Biomarkers
Bisulfite
Cancer therapies
Chemotherapy
DNA methylation
Frizzled protein
Frizzled-related protein
Frizzled-related protein 1
Gemcitabine
Gene expression
Medical prognosis
Pancreas
Patients
Plasma
Polymerase chain reaction
Prognosis
Quality of life
Survival analysis
Tumors
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Summary:No reliable predictive blood-based biomarkers are available for determining survival from pancreatic adenocarcinoma (PDAC). This combined discovery and validation study examines promoter hypermethylation (ph) of secreted frizzled-related protein 1 (SFRP1) in plasma-derived cell-free DNA as an independent prognostic marker for survival and Gemcitabine effectiveness in patients with stage IV PDAC. We conducted methylation-specific polymerase chain reaction analysis of the promoter region of the SFRP1 gene, based on bisulfite treatment. Survival was analyzed with Kaplan–Meier curves, log-rank test, and Cox regression. The discovery cohort included 40 patients, 25 receiving Gem. Gem-treated patients with phSFRP1 had a shorter median overall survival (mOS) (4.4 months) than unmethylated patients (11.6 months). Adjusted Cox-regression yielded a hazard rate (HR) of 3.48 (1.39–8.70). The validation cohort included 58 Gem-treated patients. Patients with phSFRP1 had a shorter mOS (3.2 months) than unmethylated patients (6.3 months). Adjusted Cox regression yielded an HR of 3.53 (1.85–6.74). In both cohorts, phSFRP1 was associated with poorer survival in Gem-treated patients. This may indicate that tumors with phSFRP1 are more aggressive and less sensitive to Gem treatment. This knowledge may facilitate tailored treatment of patients with stage IV PDAC. Further studies are planned to examine phSFRP1 in more intensive chemotherapy regimens.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13225717