Growth differentiation factor 15 (GDF-15) plasma levels increase during bleomycin- and cisplatin-based treatment of testicular cancer patients and relate to endothelial damage.
INTRODUCTION:Chemotherapy-related endothelial damage contributes to the early development of cardiovascular morbidity in testicular cancer patients. We aimed to identify relevant mechanisms of and search for candidate biomarkers for this endothelial damage. METHODS:Human micro-vascular endothelial c...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2015-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4295859?pdf=render |
id |
doaj-c2e0dd6f6ca04d7599dca48731444fee |
---|---|
record_format |
Article |
spelling |
doaj-c2e0dd6f6ca04d7599dca48731444fee2020-11-24T22:00:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01101e011537210.1371/journal.pone.0115372Growth differentiation factor 15 (GDF-15) plasma levels increase during bleomycin- and cisplatin-based treatment of testicular cancer patients and relate to endothelial damage.Renske AltenaRudolf S N FehrmannHink BoerElisabeth G E de VriesCoby MeijerJourik A GietemaINTRODUCTION:Chemotherapy-related endothelial damage contributes to the early development of cardiovascular morbidity in testicular cancer patients. We aimed to identify relevant mechanisms of and search for candidate biomarkers for this endothelial damage. METHODS:Human micro-vascular endothelial cells (HMEC-1) were exposed to bleomycin or cisplatin with untreated samples as control. 18k cDNA microarrays were used. Gene expression differences were analysed at single gene level and in gene sets clustered in biological pathways and validated by qRT-PCR. Protein levels of a candidate biomarker were measured in testicular cancer patient plasma before, during and after bleomycin-etoposide-cisplatin chemotherapy, and related to endothelial damage biomarkers (von Willebrand Factor (vWF), high-sensitivity C-Reactive Protein (hsCRP)). RESULTS:Microarray data identified several genes with highly differential expression; e.g. Growth Differentiation Factor 15 (GDF-15), Activating Transcription Factor 3 (ATF3) and Amphiregulin (AREG). Pathway analysis revealed strong associations with 'p53' and 'Diabetes Mellitus' gene sets. Based on known function, we measured GDF-15 protein levels in 41 testicular patients during clinical follow-up. Pre-chemotherapy GDF-15 levels equalled controls. Throughout chemotherapy GDF-15, vWF and hsCRP levels increased, and were correlated at different time-points. CONCLUSION:An unbiased approach in a preclinical model revealed genes related to chemotherapy-induced endothelial damage, like GDF-15. The increases in plasma GDF-15 levels in testicular cancer patients during chemotherapy and its association with vWF and hsCRP suggest that GDF-15 is a potentially useful biomarker related to endothelial damage.http://europepmc.org/articles/PMC4295859?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Renske Altena Rudolf S N Fehrmann Hink Boer Elisabeth G E de Vries Coby Meijer Jourik A Gietema |
spellingShingle |
Renske Altena Rudolf S N Fehrmann Hink Boer Elisabeth G E de Vries Coby Meijer Jourik A Gietema Growth differentiation factor 15 (GDF-15) plasma levels increase during bleomycin- and cisplatin-based treatment of testicular cancer patients and relate to endothelial damage. PLoS ONE |
author_facet |
Renske Altena Rudolf S N Fehrmann Hink Boer Elisabeth G E de Vries Coby Meijer Jourik A Gietema |
author_sort |
Renske Altena |
title |
Growth differentiation factor 15 (GDF-15) plasma levels increase during bleomycin- and cisplatin-based treatment of testicular cancer patients and relate to endothelial damage. |
title_short |
Growth differentiation factor 15 (GDF-15) plasma levels increase during bleomycin- and cisplatin-based treatment of testicular cancer patients and relate to endothelial damage. |
title_full |
Growth differentiation factor 15 (GDF-15) plasma levels increase during bleomycin- and cisplatin-based treatment of testicular cancer patients and relate to endothelial damage. |
title_fullStr |
Growth differentiation factor 15 (GDF-15) plasma levels increase during bleomycin- and cisplatin-based treatment of testicular cancer patients and relate to endothelial damage. |
title_full_unstemmed |
Growth differentiation factor 15 (GDF-15) plasma levels increase during bleomycin- and cisplatin-based treatment of testicular cancer patients and relate to endothelial damage. |
title_sort |
growth differentiation factor 15 (gdf-15) plasma levels increase during bleomycin- and cisplatin-based treatment of testicular cancer patients and relate to endothelial damage. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
INTRODUCTION:Chemotherapy-related endothelial damage contributes to the early development of cardiovascular morbidity in testicular cancer patients. We aimed to identify relevant mechanisms of and search for candidate biomarkers for this endothelial damage. METHODS:Human micro-vascular endothelial cells (HMEC-1) were exposed to bleomycin or cisplatin with untreated samples as control. 18k cDNA microarrays were used. Gene expression differences were analysed at single gene level and in gene sets clustered in biological pathways and validated by qRT-PCR. Protein levels of a candidate biomarker were measured in testicular cancer patient plasma before, during and after bleomycin-etoposide-cisplatin chemotherapy, and related to endothelial damage biomarkers (von Willebrand Factor (vWF), high-sensitivity C-Reactive Protein (hsCRP)). RESULTS:Microarray data identified several genes with highly differential expression; e.g. Growth Differentiation Factor 15 (GDF-15), Activating Transcription Factor 3 (ATF3) and Amphiregulin (AREG). Pathway analysis revealed strong associations with 'p53' and 'Diabetes Mellitus' gene sets. Based on known function, we measured GDF-15 protein levels in 41 testicular patients during clinical follow-up. Pre-chemotherapy GDF-15 levels equalled controls. Throughout chemotherapy GDF-15, vWF and hsCRP levels increased, and were correlated at different time-points. CONCLUSION:An unbiased approach in a preclinical model revealed genes related to chemotherapy-induced endothelial damage, like GDF-15. The increases in plasma GDF-15 levels in testicular cancer patients during chemotherapy and its association with vWF and hsCRP suggest that GDF-15 is a potentially useful biomarker related to endothelial damage. |
url |
http://europepmc.org/articles/PMC4295859?pdf=render |
work_keys_str_mv |
AT renskealtena growthdifferentiationfactor15gdf15plasmalevelsincreaseduringbleomycinandcisplatinbasedtreatmentoftesticularcancerpatientsandrelatetoendothelialdamage AT rudolfsnfehrmann growthdifferentiationfactor15gdf15plasmalevelsincreaseduringbleomycinandcisplatinbasedtreatmentoftesticularcancerpatientsandrelatetoendothelialdamage AT hinkboer growthdifferentiationfactor15gdf15plasmalevelsincreaseduringbleomycinandcisplatinbasedtreatmentoftesticularcancerpatientsandrelatetoendothelialdamage AT elisabethgedevries growthdifferentiationfactor15gdf15plasmalevelsincreaseduringbleomycinandcisplatinbasedtreatmentoftesticularcancerpatientsandrelatetoendothelialdamage AT cobymeijer growthdifferentiationfactor15gdf15plasmalevelsincreaseduringbleomycinandcisplatinbasedtreatmentoftesticularcancerpatientsandrelatetoendothelialdamage AT jourikagietema growthdifferentiationfactor15gdf15plasmalevelsincreaseduringbleomycinandcisplatinbasedtreatmentoftesticularcancerpatientsandrelatetoendothelialdamage |
_version_ |
1725845307978153984 |