Cell Senescence-Related Pathways Are Enriched in Breast Cancer Patients With Late Toxicity After Radiotherapy and Low Radiation-Induced Lymphocyte Apoptosis

Background: Radiation-induced late effects are a common cause of morbidity among cancer survivors. The biomarker with the best evidence as a predictive test of late reactions is the radiation-induced lymphocyte apoptosis (RILA) assay. We aimed to investigate the molecular basis underlying the distin...

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Authors: Aguado-Flor E., Fuentes-Raspall M.J., Gonzalo R., Alonso C., Ramón y Cajal T., Fisas D., Seoane A., Sánchez-Pla Á., Giralt J., Díez O., Gutiérrez-Enríquez S.
Format: article
Status:Published version
Publication Date:2022
Country:España
Institution:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repository:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
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Online Access:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=15826
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85131859157&doi=10.3389%2ffonc.2022.825703&partnerID=40&md5=0e5fe416e18734469fa8817fb22805b9
Access Level:Open access
Keyword:complementary DNA
G protein coupled receptor
interferon
messenger RNA
transcription factor
transcriptome
adult
Article
blood sampling
body mass
brachytherapy
breast cancer
cancer hormone therapy
cancer radiotherapy
cell aging
cell culture
cell cycle
cell isolation
clinical article
down regulation
erythema
female
fibrosis
gene expression
gene expression profiling
gene set enrichment analysis
histology
human
immunocompetent cell
in vitro study
interferon signaling
microarray analysis
NF kB signaling
peripheral blood mononuclear cell
phenotype
radiation dose
radiation induced lymphocyte apoptosis assay
radioassay
reverse transcription polymerase chain reaction
skin toxicity
smoking
upregulation
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spelling Cell Senescence-Related Pathways Are Enriched in Breast Cancer Patients With Late Toxicity After Radiotherapy and Low Radiation-Induced Lymphocyte ApoptosisAguado-Flor E.Fuentes-Raspall M.J.Gonzalo R.Alonso C.Ramón y Cajal T.Fisas D.Seoane A.Sánchez-Pla Á.Giralt J.Díez O.Gutiérrez-Enríquez S.complementary DNAG protein coupled receptorinterferonmessenger RNAtranscription factortranscriptomeadultArticleblood samplingbody massbrachytherapybreast cancercancer hormone therapycancer radiotherapycell agingcell culturecell cyclecell isolationclinical articledown regulationerythemafemalefibrosisgene expressiongene expression profilinggene set enrichment analysishistologyhumanimmunocompetent cellin vitro studyinterferon signalingmicroarray analysisNF kB signalingperipheral blood mononuclear cellphenotyperadiation doseradiation induced lymphocyte apoptosis assayradioassayreverse transcription polymerase chain reactionskin toxicitysmokingupregulationBackground: Radiation-induced late effects are a common cause of morbidity among cancer survivors. The biomarker with the best evidence as a predictive test of late reactions is the radiation-induced lymphocyte apoptosis (RILA) assay. We aimed to investigate the molecular basis underlying the distinctive RILA levels by using gene expression analysis in patients with and without late effects and in whom we had also first identified differences in RILA levels. Patients and Methods: Peripheral blood mononuclear cells of 10 patients with late severe skin complications and 10 patients without symptoms, selected from those receiving radiotherapy from 1993 to 2007, were mock-irradiated or irradiated with 8 Gy. The 48-h response was analyzed in parallel by RILA assay and gene expression profiling with Affymetrix microarrays. Irradiated and non-irradiated gene expression profiles were compared between both groups. Gene set enrichment analysis was performed to identify differentially expressed biological processes. Results: Although differentially expressed mRNAs did not reach a significant adjusted p-value between patients suffering and not suffering clinical toxicity, the enriched pathways indicated significant differences between the two groups, either in irradiated or non-irradiated cells. In basal conditions, the main differentially expressed pathways between the toxicity and non-toxicity groups were the transport of small molecules, interferon signaling, and transcription. After 8 Gy, the differences lay in pathways highly related to cell senescence like cell cycle/NF-?B, G-protein-coupled receptors, and interferon signaling. Conclusion: Patients at risk of developing late toxicity have a distinctive pathway signature driven by deregulation of immune and cell cycle pathways related to senescence, which in turn may underlie their low RILA phenotype. Copyright © 2022 Aguado-Flor, Fuentes-Raspall, Gonzalo, Alonso, Ramón y Cajal, Fisas, Seoane, Sánchez-Pla, Giralt, Díez and Gutiérrez-Enríquez.FRONTIERS MEDIA SA2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=15826https://www.scopus.com/inward/record.uri?eid=2-s2.0-85131859157&doi=10.3389%2ffonc.2022.825703&partnerID=40&md5=0e5fe416e18734469fa8817fb22805b9Frontiers in OncologyISSN: 2234943Xreponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p158262026-06-14T12:41:47Z
dc.title.none.fl_str_mv Cell Senescence-Related Pathways Are Enriched in Breast Cancer Patients With Late Toxicity After Radiotherapy and Low Radiation-Induced Lymphocyte Apoptosis
title Cell Senescence-Related Pathways Are Enriched in Breast Cancer Patients With Late Toxicity After Radiotherapy and Low Radiation-Induced Lymphocyte Apoptosis
spellingShingle Cell Senescence-Related Pathways Are Enriched in Breast Cancer Patients With Late Toxicity After Radiotherapy and Low Radiation-Induced Lymphocyte Apoptosis
Aguado-Flor E.
complementary DNA
G protein coupled receptor
interferon
messenger RNA
transcription factor
transcriptome
adult
Article
blood sampling
body mass
brachytherapy
breast cancer
cancer hormone therapy
cancer radiotherapy
cell aging
cell culture
cell cycle
cell isolation
clinical article
down regulation
erythema
female
fibrosis
gene expression
gene expression profiling
gene set enrichment analysis
histology
human
immunocompetent cell
in vitro study
interferon signaling
microarray analysis
NF kB signaling
peripheral blood mononuclear cell
phenotype
radiation dose
radiation induced lymphocyte apoptosis assay
radioassay
reverse transcription polymerase chain reaction
skin toxicity
smoking
upregulation
title_short Cell Senescence-Related Pathways Are Enriched in Breast Cancer Patients With Late Toxicity After Radiotherapy and Low Radiation-Induced Lymphocyte Apoptosis
title_full Cell Senescence-Related Pathways Are Enriched in Breast Cancer Patients With Late Toxicity After Radiotherapy and Low Radiation-Induced Lymphocyte Apoptosis
title_fullStr Cell Senescence-Related Pathways Are Enriched in Breast Cancer Patients With Late Toxicity After Radiotherapy and Low Radiation-Induced Lymphocyte Apoptosis
title_full_unstemmed Cell Senescence-Related Pathways Are Enriched in Breast Cancer Patients With Late Toxicity After Radiotherapy and Low Radiation-Induced Lymphocyte Apoptosis
title_sort Cell Senescence-Related Pathways Are Enriched in Breast Cancer Patients With Late Toxicity After Radiotherapy and Low Radiation-Induced Lymphocyte Apoptosis
dc.creator.none.fl_str_mv Aguado-Flor E.
Fuentes-Raspall M.J.
Gonzalo R.
Alonso C.
Ramón y Cajal T.
Fisas D.
Seoane A.
Sánchez-Pla Á.
Giralt J.
Díez O.
Gutiérrez-Enríquez S.
author Aguado-Flor E.
author_facet Aguado-Flor E.
Fuentes-Raspall M.J.
Gonzalo R.
Alonso C.
Ramón y Cajal T.
Fisas D.
Seoane A.
Sánchez-Pla Á.
Giralt J.
Díez O.
Gutiérrez-Enríquez S.
author_role author
author2 Fuentes-Raspall M.J.
Gonzalo R.
Alonso C.
Ramón y Cajal T.
Fisas D.
Seoane A.
Sánchez-Pla Á.
Giralt J.
Díez O.
Gutiérrez-Enríquez S.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv complementary DNA
G protein coupled receptor
interferon
messenger RNA
transcription factor
transcriptome
adult
Article
blood sampling
body mass
brachytherapy
breast cancer
cancer hormone therapy
cancer radiotherapy
cell aging
cell culture
cell cycle
cell isolation
clinical article
down regulation
erythema
female
fibrosis
gene expression
gene expression profiling
gene set enrichment analysis
histology
human
immunocompetent cell
in vitro study
interferon signaling
microarray analysis
NF kB signaling
peripheral blood mononuclear cell
phenotype
radiation dose
radiation induced lymphocyte apoptosis assay
radioassay
reverse transcription polymerase chain reaction
skin toxicity
smoking
upregulation
topic complementary DNA
G protein coupled receptor
interferon
messenger RNA
transcription factor
transcriptome
adult
Article
blood sampling
body mass
brachytherapy
breast cancer
cancer hormone therapy
cancer radiotherapy
cell aging
cell culture
cell cycle
cell isolation
clinical article
down regulation
erythema
female
fibrosis
gene expression
gene expression profiling
gene set enrichment analysis
histology
human
immunocompetent cell
in vitro study
interferon signaling
microarray analysis
NF kB signaling
peripheral blood mononuclear cell
phenotype
radiation dose
radiation induced lymphocyte apoptosis assay
radioassay
reverse transcription polymerase chain reaction
skin toxicity
smoking
upregulation
description Background: Radiation-induced late effects are a common cause of morbidity among cancer survivors. The biomarker with the best evidence as a predictive test of late reactions is the radiation-induced lymphocyte apoptosis (RILA) assay. We aimed to investigate the molecular basis underlying the distinctive RILA levels by using gene expression analysis in patients with and without late effects and in whom we had also first identified differences in RILA levels. Patients and Methods: Peripheral blood mononuclear cells of 10 patients with late severe skin complications and 10 patients without symptoms, selected from those receiving radiotherapy from 1993 to 2007, were mock-irradiated or irradiated with 8 Gy. The 48-h response was analyzed in parallel by RILA assay and gene expression profiling with Affymetrix microarrays. Irradiated and non-irradiated gene expression profiles were compared between both groups. Gene set enrichment analysis was performed to identify differentially expressed biological processes. Results: Although differentially expressed mRNAs did not reach a significant adjusted p-value between patients suffering and not suffering clinical toxicity, the enriched pathways indicated significant differences between the two groups, either in irradiated or non-irradiated cells. In basal conditions, the main differentially expressed pathways between the toxicity and non-toxicity groups were the transport of small molecules, interferon signaling, and transcription. After 8 Gy, the differences lay in pathways highly related to cell senescence like cell cycle/NF-?B, G-protein-coupled receptors, and interferon signaling. Conclusion: Patients at risk of developing late toxicity have a distinctive pathway signature driven by deregulation of immune and cell cycle pathways related to senescence, which in turn may underlie their low RILA phenotype. Copyright © 2022 Aguado-Flor, Fuentes-Raspall, Gonzalo, Alonso, Ramón y Cajal, Fisas, Seoane, Sánchez-Pla, Giralt, Díez and Gutiérrez-Enríquez.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=15826
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85131859157&doi=10.3389%2ffonc.2022.825703&partnerID=40&md5=0e5fe416e18734469fa8817fb22805b9
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=15826
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85131859157&doi=10.3389%2ffonc.2022.825703&partnerID=40&md5=0e5fe416e18734469fa8817fb22805b9
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv FRONTIERS MEDIA SA
publisher.none.fl_str_mv FRONTIERS MEDIA SA
dc.source.none.fl_str_mv Frontiers in Oncology
ISSN: 2234943X
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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