TY - JOUR

T1 - Promoter hypermethylation of SFRP1 as a prognostic and potentially predictive blood-based biomarker in patients with localized pancreatic ductal adenocarcinoma

AU - Stubbe, Benjamin Emil

AU - Larsen, Anders Christian

AU - Madsen, Poul Henning

AU - Krarup, Henrik Bygum

AU - Pedersen, Inge Søkilde

AU - Lundbye-Christensen, Søren

AU - Hansen, Carsten Palnæs

AU - Hasselby, Jane Preuss

AU - Johansen, Astrid Zedlitz

AU - Thorlacius-Ussing, Ole

AU - Johansen, Julia Sidenius

AU - Henriksen, Stine Dam

N1 - Publisher Copyright: Copyright © 2023 Stubbe, Larsen, Madsen, Krarup, Pedersen, Lundbye-Christensen, Hansen, Hasselby, Johansen, Thorlacius-Ussing, Johansen and Henriksen.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - biomarker

KW - blood-based

KW - cfDNA

KW - DNA methylation

KW - epigenetic

KW - pancreatic cancer

KW - personalized therapy

KW - survival

UR - http://www.scopus.com/inward/record.url?scp=85162043526&partnerID=8YFLogxK

U2 - 10.3389/fonc.2023.1211292

DO - 10.3389/fonc.2023.1211292

M3 - Journal article

C2 - 37333823

AN - SCOPUS:85162043526

VL - 13

JO - Frontiers in Oncology

JF - Frontiers in Oncology

SN - 2234-943X

M1 - 1211292

ER -