Validation of SFRP1 Promoter Hypermethylation in Plasma as a Prognostic Marker for Survival and Gemcitabine Effectiveness in Patients with Stage IV Pancreatic Adenocarcinoma

No reliable predictive blood-based biomarkers are available for determining survival from pancreatic adenocarcinoma (PDAC). This combined discovery and validation study examines promoter hypermethylation (ph) of secreted frizzled-related protein 1 (SFRP1) in plasma-derived cell-free DNA as an indepe...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Benjamin Emil Stubbe, Stine Dam Henriksen, Poul Henning Madsen, Anders Christian Larsen, Henrik Bygum Krarup, Inge Søkilde Pedersen, Martin Nygård Johansen, Ole Thorlacius-Ussing
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	biomarker cancer pancreatic cancer prognostic survival blood-based Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/6057e4d7ae15449b8123c6666d98c261
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6057e4d7ae15449b8123c6666d98c261
record_format	dspace
spelling	oai:doaj.org-article:6057e4d7ae15449b8123c6666d98c2612021-11-25T17:03:12ZValidation of SFRP1 Promoter Hypermethylation in Plasma as a Prognostic Marker for Survival and Gemcitabine Effectiveness in Patients with Stage IV Pancreatic Adenocarcinoma10.3390/cancers132257172072-6694https://doaj.org/article/6057e4d7ae15449b8123c6666d98c2612021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5717https://doaj.org/toc/2072-6694No reliable predictive blood-based biomarkers are available for determining survival from pancreatic adenocarcinoma (PDAC). This combined discovery and validation study examines promoter hypermethylation (ph) of secreted frizzled-related protein 1 (SFRP1) in plasma-derived cell-free DNA as an independent prognostic marker for survival and Gemcitabine effectiveness in patients with stage IV PDAC. We conducted methylation-specific polymerase chain reaction analysis of the promoter region of the SFRP1 gene, based on bisulfite treatment. Survival was analyzed with Kaplan–Meier curves, log-rank test, and Cox regression. The discovery cohort included 40 patients, 25 receiving Gem. Gem-treated patients with phSFRP1 had a shorter median overall survival (mOS) (4.4 months) than unmethylated patients (11.6 months). Adjusted Cox-regression yielded a hazard rate (HR) of 3.48 (1.39–8.70). The validation cohort included 58 Gem-treated patients. Patients with phSFRP1 had a shorter mOS (3.2 months) than unmethylated patients (6.3 months). Adjusted Cox regression yielded an HR of 3.53 (1.85–6.74). In both cohorts, phSFRP1 was associated with poorer survival in Gem-treated patients. This may indicate that tumors with phSFRP1 are more aggressive and less sensitive to Gem treatment. This knowledge may facilitate tailored treatment of patients with stage IV PDAC. Further studies are planned to examine phSFRP1 in more intensive chemotherapy regimens.Benjamin Emil StubbeStine Dam HenriksenPoul Henning MadsenAnders Christian LarsenHenrik Bygum KrarupInge Søkilde PedersenMartin Nygård JohansenOle Thorlacius-UssingMDPI AGarticlebiomarkercancerpancreatic cancerprognosticsurvivalblood-basedNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5717, p 5717 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	biomarker cancer pancreatic cancer prognostic survival blood-based Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	biomarker cancer pancreatic cancer prognostic survival blood-based Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Benjamin Emil Stubbe Stine Dam Henriksen Poul Henning Madsen Anders Christian Larsen Henrik Bygum Krarup Inge Søkilde Pedersen Martin Nygård Johansen Ole Thorlacius-Ussing Validation of SFRP1 Promoter Hypermethylation in Plasma as a Prognostic Marker for Survival and Gemcitabine Effectiveness in Patients with Stage IV Pancreatic Adenocarcinoma
description	No reliable predictive blood-based biomarkers are available for determining survival from pancreatic adenocarcinoma (PDAC). This combined discovery and validation study examines promoter hypermethylation (ph) of secreted frizzled-related protein 1 (SFRP1) in plasma-derived cell-free DNA as an independent prognostic marker for survival and Gemcitabine effectiveness in patients with stage IV PDAC. We conducted methylation-specific polymerase chain reaction analysis of the promoter region of the SFRP1 gene, based on bisulfite treatment. Survival was analyzed with Kaplan–Meier curves, log-rank test, and Cox regression. The discovery cohort included 40 patients, 25 receiving Gem. Gem-treated patients with phSFRP1 had a shorter median overall survival (mOS) (4.4 months) than unmethylated patients (11.6 months). Adjusted Cox-regression yielded a hazard rate (HR) of 3.48 (1.39–8.70). The validation cohort included 58 Gem-treated patients. Patients with phSFRP1 had a shorter mOS (3.2 months) than unmethylated patients (6.3 months). Adjusted Cox regression yielded an HR of 3.53 (1.85–6.74). In both cohorts, phSFRP1 was associated with poorer survival in Gem-treated patients. This may indicate that tumors with phSFRP1 are more aggressive and less sensitive to Gem treatment. This knowledge may facilitate tailored treatment of patients with stage IV PDAC. Further studies are planned to examine phSFRP1 in more intensive chemotherapy regimens.
format	article
author	Benjamin Emil Stubbe Stine Dam Henriksen Poul Henning Madsen Anders Christian Larsen Henrik Bygum Krarup Inge Søkilde Pedersen Martin Nygård Johansen Ole Thorlacius-Ussing
author_facet	Benjamin Emil Stubbe Stine Dam Henriksen Poul Henning Madsen Anders Christian Larsen Henrik Bygum Krarup Inge Søkilde Pedersen Martin Nygård Johansen Ole Thorlacius-Ussing
author_sort	Benjamin Emil Stubbe
title	Validation of SFRP1 Promoter Hypermethylation in Plasma as a Prognostic Marker for Survival and Gemcitabine Effectiveness in Patients with Stage IV Pancreatic Adenocarcinoma
title_short	Validation of SFRP1 Promoter Hypermethylation in Plasma as a Prognostic Marker for Survival and Gemcitabine Effectiveness in Patients with Stage IV Pancreatic Adenocarcinoma
title_full	Validation of SFRP1 Promoter Hypermethylation in Plasma as a Prognostic Marker for Survival and Gemcitabine Effectiveness in Patients with Stage IV Pancreatic Adenocarcinoma
title_fullStr	Validation of SFRP1 Promoter Hypermethylation in Plasma as a Prognostic Marker for Survival and Gemcitabine Effectiveness in Patients with Stage IV Pancreatic Adenocarcinoma
title_full_unstemmed	Validation of SFRP1 Promoter Hypermethylation in Plasma as a Prognostic Marker for Survival and Gemcitabine Effectiveness in Patients with Stage IV Pancreatic Adenocarcinoma
title_sort	validation of sfrp1 promoter hypermethylation in plasma as a prognostic marker for survival and gemcitabine effectiveness in patients with stage iv pancreatic adenocarcinoma
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6057e4d7ae15449b8123c6666d98c261
work_keys_str_mv	AT benjaminemilstubbe validationofsfrp1promoterhypermethylationinplasmaasaprognosticmarkerforsurvivalandgemcitabineeffectivenessinpatientswithstageivpancreaticadenocarcinoma AT stinedamhenriksen validationofsfrp1promoterhypermethylationinplasmaasaprognosticmarkerforsurvivalandgemcitabineeffectivenessinpatientswithstageivpancreaticadenocarcinoma AT poulhenningmadsen validationofsfrp1promoterhypermethylationinplasmaasaprognosticmarkerforsurvivalandgemcitabineeffectivenessinpatientswithstageivpancreaticadenocarcinoma AT anderschristianlarsen validationofsfrp1promoterhypermethylationinplasmaasaprognosticmarkerforsurvivalandgemcitabineeffectivenessinpatientswithstageivpancreaticadenocarcinoma AT henrikbygumkrarup validationofsfrp1promoterhypermethylationinplasmaasaprognosticmarkerforsurvivalandgemcitabineeffectivenessinpatientswithstageivpancreaticadenocarcinoma AT ingesøkildepedersen validationofsfrp1promoterhypermethylationinplasmaasaprognosticmarkerforsurvivalandgemcitabineeffectivenessinpatientswithstageivpancreaticadenocarcinoma AT martinnygardjohansen validationofsfrp1promoterhypermethylationinplasmaasaprognosticmarkerforsurvivalandgemcitabineeffectivenessinpatientswithstageivpancreaticadenocarcinoma AT olethorlaciusussing validationofsfrp1promoterhypermethylationinplasmaasaprognosticmarkerforsurvivalandgemcitabineeffectivenessinpatientswithstageivpancreaticadenocarcinoma
_version_	1718412777215754240

Validation of SFRP1 Promoter Hypermethylation in Plasma as a Prognostic Marker for Survival and Gemcitabine Effectiveness in Patients with Stage IV Pancreatic Adenocarcinoma

Ejemplares similares