Frontiers in Oncology (Jun 2023)

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

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

DOI
https://doi.org/10.3389/fonc.2023.1211292
Journal volume & issue
Vol. 13

Abstract

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IntroductionCurrent 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.MethodsBased 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.ResultsThe 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.DiscussionResults 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.

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