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...
| Autores: | , , , , , , , , , , |
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| Tipo de documento: | artigo |
| Estado: | Versão publicada |
| Data de publicação: | 2022 |
| País: | España |
| Recursos: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repositório: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p15826 |
| Acesso em linha: | 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: | Acceso aberto |
| Palavra-chave: | 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 |
| Resumo: | 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. |
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