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

Frontiers in Oncology

Oncology

Poul Henning Madsen¹  Henrik Bygum Krarup¹  Anders Christian Larsen²  Inge Søkilde Pedersen³  Stine Dam Henriksen⁴  Benjamin Emil Stubbe⁴  Ole Thorlacius-Ussing⁴  Astrid Zedlitz Johansen⁵  Julia Sidenius Johansen⁶  Jane Preuss Hasselby⁷  Carsten Palnæs Hansen⁸  Søren Lundbye-Christensen⁹ 

[1] Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark;Department of Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark;Department of Clinical Medicine, Aalborg University, Aalborg, Denmark;Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark;Department of Clinical Medicine, Aalborg University, Aalborg, Denmark;Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark;Department of Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark;Department of Gastrointestinal Surgery, Aalborg University Hospital, Aalborg, Denmark;Department of Clinical Medicine, Aalborg University, Aalborg, Denmark;Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark;Department of Oncology, Copenhagen University Hospital – Herlev and Gentofte, Herlev, Denmark;Department of Oncology, Copenhagen University Hospital – Herlev and Gentofte, Herlev, Denmark;Department of Medicine, Copenhagen University Hospital – Herlev and Gentofte, Herlev, Denmark;Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;Department of Pathology, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark;Department of Surgery, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark;Unit of Clinical Biostatistics, Aalborg University Hospital, Aalborg, Denmark;

关键词: biomarker;    pancreatic cancer;    survival;    epigenetic;    DNA methylation;    personalized therapy;    blood-based;    cfDNA;   

DOI  :  10.3389/fonc.2023.1211292

 received in 2023-04-24, accepted in 2023-05-22,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

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