Promoter hypermethylation of SFRP1 as a prognostic and potentially predictive blood-based biomarker in patients with localized pancreatic ductal adenocarcinoma
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...
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1211292/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Benjamin Emil Stubbe |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T07:56:39Z |
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| institution | Directory Open Access Journal |
| issn | 2234-943X |
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| last_indexed | 2024-03-13T07:56:39Z |
| publishDate | 2023-06-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-f44347b6f1ea445e969725de09fab1802023-06-02T05:14:50ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-06-011310.3389/fonc.2023.12112921211292Promoter hypermethylation of SFRP1 as a prognostic and potentially predictive blood-based biomarker in patients with localized pancreatic ductal adenocarcinomaBenjamin Emil Stubbe0Benjamin Emil Stubbe1Benjamin Emil Stubbe2Anders Christian Larsen3Anders Christian Larsen4Poul Henning Madsen5Poul Henning Madsen6Henrik Bygum Krarup7Henrik Bygum Krarup8Inge Søkilde Pedersen9Inge Søkilde Pedersen10Inge Søkilde Pedersen11Søren Lundbye-Christensen12Carsten Palnæs Hansen13Jane Preuss Hasselby14Astrid Zedlitz Johansen15Ole Thorlacius-Ussing16Ole Thorlacius-Ussing17Ole Thorlacius-Ussing18Julia Sidenius Johansen19Julia Sidenius Johansen20Julia Sidenius Johansen21Stine Dam Henriksen22Stine Dam Henriksen23Stine Dam Henriksen24Department of Gastrointestinal Surgery, Aalborg University Hospital, Aalborg, DenmarkDepartment of Clinical Medicine, Aalborg University, Aalborg, DenmarkClinical Cancer Research Center, Aalborg University Hospital, Aalborg, DenmarkDepartment of Clinical Medicine, Aalborg University, Aalborg, DenmarkClinical Cancer Research Center, Aalborg University Hospital, Aalborg, DenmarkClinical Cancer Research Center, Aalborg University Hospital, Aalborg, DenmarkDepartment of Molecular Diagnostics, Aalborg University Hospital, Aalborg, DenmarkClinical Cancer Research Center, Aalborg University Hospital, Aalborg, DenmarkDepartment of Molecular Diagnostics, Aalborg University Hospital, Aalborg, DenmarkDepartment of Clinical Medicine, Aalborg University, Aalborg, DenmarkClinical Cancer Research Center, Aalborg University Hospital, Aalborg, DenmarkDepartment of Molecular Diagnostics, Aalborg University Hospital, Aalborg, DenmarkUnit of Clinical Biostatistics, Aalborg University Hospital, Aalborg, DenmarkDepartment of Surgery, Copenhagen University Hospital - Rigshospitalet, Copenhagen, DenmarkDepartment of Pathology, Copenhagen University Hospital – Rigshospitalet, Copenhagen, DenmarkDepartment of Oncology, Copenhagen University Hospital – Herlev and Gentofte, Herlev, DenmarkDepartment of Gastrointestinal Surgery, Aalborg University Hospital, Aalborg, DenmarkDepartment of Clinical Medicine, Aalborg University, Aalborg, DenmarkClinical Cancer Research Center, Aalborg University Hospital, Aalborg, DenmarkDepartment of Oncology, Copenhagen University Hospital – Herlev and Gentofte, Herlev, DenmarkDepartment of Medicine, Copenhagen University Hospital – Herlev and Gentofte, Herlev, Denmark0Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Gastrointestinal Surgery, Aalborg University Hospital, Aalborg, DenmarkDepartment of Clinical Medicine, Aalborg University, Aalborg, DenmarkClinical Cancer Research Center, Aalborg University Hospital, Aalborg, DenmarkIntroductionCurrent 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.https://www.frontiersin.org/articles/10.3389/fonc.2023.1211292/fullbiomarkerpancreatic cancersurvivalepigeneticDNA methylationpersonalized therapy |
| spellingShingle | 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 Promoter hypermethylation of SFRP1 as a prognostic and potentially predictive blood-based biomarker in patients with localized pancreatic ductal adenocarcinoma Frontiers in Oncology biomarker pancreatic cancer survival epigenetic DNA methylation personalized therapy |
| title | Promoter hypermethylation of SFRP1 as a prognostic and potentially predictive blood-based biomarker in patients with localized pancreatic ductal adenocarcinoma |
| title_full | Promoter hypermethylation of SFRP1 as a prognostic and potentially predictive blood-based biomarker in patients with localized pancreatic ductal adenocarcinoma |
| title_fullStr | Promoter hypermethylation of SFRP1 as a prognostic and potentially predictive blood-based biomarker in patients with localized pancreatic ductal adenocarcinoma |
| title_full_unstemmed | Promoter hypermethylation of SFRP1 as a prognostic and potentially predictive blood-based biomarker in patients with localized pancreatic ductal adenocarcinoma |
| title_short | Promoter hypermethylation of SFRP1 as a prognostic and potentially predictive blood-based biomarker in patients with localized pancreatic ductal adenocarcinoma |
| title_sort | promoter hypermethylation of sfrp1 as a prognostic and potentially predictive blood based biomarker in patients with localized pancreatic ductal adenocarcinoma |
| topic | biomarker pancreatic cancer survival epigenetic DNA methylation personalized therapy |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1211292/full |
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