Promoter hypermethylation of SFRP1 as a prognostic and potentially predictive blood-based biomarker in patients with localized pancreatic ductal adenocarcinoma

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  • Benjamin Emil Stubbe
  • Anders Christian Larsen
  • Poul Henning Madsen
  • Henrik Bygum Krarup
  • Inge Søkilde Pedersen
  • Søren Lundbye-Christensen
  • Carsten Palnæs Hansen
  • Hasselby, Jane Preuss
  • Astrid Zedlitz Johansen
  • Ole Thorlacius-Ussing
  • Johansen, Julia Sidenius
  • Stine Dam Henriksen

Introduction: Current prognostic blood-based biomarkers for pancreatic adenocarcinoma (PDAC) are limited. Recently, promoter hypermethylation of SFRP1 (phSFRP1) has been linked to poor prognosis in patients with gemcitabine-treated stage IV PDAC. This study explores the effects of phSFRP1 in patients with lower stage PDAC. Methods: Based on a bisulfite treatment process, the promoter region of the SFRP1 gene was analyzed with methylation-specific PCR. Kaplan-Meier curves, log-rank tests, and generalized linear regression analysis were used to assess restricted mean survival time survival at 12 and 24 months. Results: The study included 211 patients with stage I-II PDAC. The median overall survival of patients with phSFRP1 was 13.1 months, compared to 19.6 months in patients with unmethylated SFRP1 (umSFRP1). In adjusted analysis, phSFRP1 was associated with a loss of 1.15 months (95%CI -2.11, -0.20) and 2.71 months (95%CI -2.71, -0.45) of life at 12 and 24 months, respectively. There was no significant effect of phSFRP1 on disease-free or progression-free survival. In stage I-II PDAC, patients with phSFRP1 have worse prognoses than patients with umSFRP1. Discussion: Results could indicate that the poor prognosis may be caused by reduced benefit from adjuvant chemotherapy. SFRP1 may help guide the clinician and be a possible target for epigenetically modifying drugs.

OriginalsprogEngelsk
Artikelnummer1211292
TidsskriftFrontiers in Oncology
Vol/bind13
Antal sider11
ISSN2234-943X
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This study was supported by two private foundations: The Speciallæge Heinrich Kopps foundation and the Svend Andersen Foundation. Acknowledgments

Publisher Copyright:
Copyright © 2023 Stubbe, Larsen, Madsen, Krarup, Pedersen, Lundbye-Christensen, Hansen, Hasselby, Johansen, Thorlacius-Ussing, Johansen and Henriksen.

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