Cell Senescence-Related Pathways Are Enriched in Breast Cancer Patients With Late Toxicity After Radiotherapy and Low Radiation-Induced Lymphocyte Apoptosis
BackgroundRadiation-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 distinct...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.825703/full |
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| author | Ester Aguado-Flor María J. Fuentes-Raspall Ricardo Gonzalo Carmen Alonso Teresa Ramón y Cajal David Fisas Alejandro Seoane Álex Sánchez-Pla Álex Sánchez-Pla Jordi Giralt Jordi Giralt Orland Díez Orland Díez Sara Gutiérrez-Enríquez |
| author_facet | Ester Aguado-Flor María J. Fuentes-Raspall Ricardo Gonzalo Carmen Alonso Teresa Ramón y Cajal David Fisas Alejandro Seoane Álex Sánchez-Pla Álex Sánchez-Pla Jordi Giralt Jordi Giralt Orland Díez Orland Díez Sara Gutiérrez-Enríquez |
| author_sort | Ester Aguado-Flor |
| collection | DOAJ |
| description | BackgroundRadiation-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 MethodsPeripheral 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.ResultsAlthough 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-κB, G-protein-coupled receptors, and interferon signaling.ConclusionPatients 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. |
| first_indexed | 2024-12-12T08:56:31Z |
| format | Article |
| id | doaj.art-7c6649b3bb71437fb465a5121872248c |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-12T08:56:31Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-7c6649b3bb71437fb465a5121872248c2022-12-22T00:29:59ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-05-011210.3389/fonc.2022.825703825703Cell Senescence-Related Pathways Are Enriched in Breast Cancer Patients With Late Toxicity After Radiotherapy and Low Radiation-Induced Lymphocyte ApoptosisEster Aguado-Flor0María J. Fuentes-Raspall1Ricardo Gonzalo2Carmen Alonso3Teresa Ramón y Cajal4David Fisas5Alejandro Seoane6Álex Sánchez-Pla7Álex Sánchez-Pla8Jordi Giralt9Jordi Giralt10Orland Díez11Orland Díez12Sara Gutiérrez-Enríquez13Hereditary Cancer Genetics Group, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Barcelona, SpainRadiation Oncology Department, Santa Creu i Sant Pau Hospital, Barcelona, SpainStatistics and Bioinformatics Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona, SpainMedical Oncology Department, Santa Creu i Sant Pau Hospital, Barcelona, SpainMedical Oncology Department, Santa Creu i Sant Pau Hospital, Barcelona, SpainMedical Oncology Department, Santa Creu i Sant Pau Hospital, Barcelona, SpainMedical Physics Department, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona, SpainStatistics and Bioinformatics Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona, SpainGenetics, Microbiology and Statistics Department, Universitat de Barcelona, Barcelona, SpainRadiation Oncology Department, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona, SpainRadiation Oncology Group, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Barcelona, SpainHereditary Cancer Genetics Group, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Barcelona, SpainArea of Clinical and Molecular Genetics, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona, SpainHereditary Cancer Genetics Group, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Barcelona, SpainBackgroundRadiation-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 MethodsPeripheral 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.ResultsAlthough 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-κB, G-protein-coupled receptors, and interferon signaling.ConclusionPatients 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.https://www.frontiersin.org/articles/10.3389/fonc.2022.825703/fullradiotherapy—adverse effectsradiation-induced lymphocyte apoptosis (RILA)gene set enrichment analysis (GSEA)late skin toxicitybreast cancer |
| spellingShingle | Ester Aguado-Flor María J. Fuentes-Raspall Ricardo Gonzalo Carmen Alonso Teresa Ramón y Cajal David Fisas Alejandro Seoane Álex Sánchez-Pla Álex Sánchez-Pla Jordi Giralt Jordi Giralt Orland Díez Orland Díez Sara Gutiérrez-Enríquez Cell Senescence-Related Pathways Are Enriched in Breast Cancer Patients With Late Toxicity After Radiotherapy and Low Radiation-Induced Lymphocyte Apoptosis Frontiers in Oncology radiotherapy—adverse effects radiation-induced lymphocyte apoptosis (RILA) gene set enrichment analysis (GSEA) late skin toxicity breast cancer |
| title | 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_short | 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 |
| topic | radiotherapy—adverse effects radiation-induced lymphocyte apoptosis (RILA) gene set enrichment analysis (GSEA) late skin toxicity breast cancer |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.825703/full |
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