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A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity

The quest for the discovery and validation of radiosensitivity biomarkers is ongoing and while conventional bioassays are well established as biomarkers, molecular advances have unveiled new emerging biomarkers. Herein, we present the validation of a new 4-gene signature panel of CDKN1, FDXR, SESN1...

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Autores principales: Howe, Orla, White, Lisa, Cullen, Daniel, O’Brien, Grainne, Shields, Laura, Bryant, Jane, Noone, Emma, Bradshaw, Shirley, Finn, Marie, Dunne, Mary, Shannon, Aoife M., Armstrong, John, McClean, Brendan, Meade, Aidan, Badie, Christophe, Lyng, Fiona M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508881/
https://www.ncbi.nlm.nih.gov/pubmed/34638945
http://dx.doi.org/10.3390/ijms221910607
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author Howe, Orla
White, Lisa
Cullen, Daniel
O’Brien, Grainne
Shields, Laura
Bryant, Jane
Noone, Emma
Bradshaw, Shirley
Finn, Marie
Dunne, Mary
Shannon, Aoife M.
Armstrong, John
McClean, Brendan
Meade, Aidan
Badie, Christophe
Lyng, Fiona M.
author_facet Howe, Orla
White, Lisa
Cullen, Daniel
O’Brien, Grainne
Shields, Laura
Bryant, Jane
Noone, Emma
Bradshaw, Shirley
Finn, Marie
Dunne, Mary
Shannon, Aoife M.
Armstrong, John
McClean, Brendan
Meade, Aidan
Badie, Christophe
Lyng, Fiona M.
author_sort Howe, Orla
collection PubMed
description The quest for the discovery and validation of radiosensitivity biomarkers is ongoing and while conventional bioassays are well established as biomarkers, molecular advances have unveiled new emerging biomarkers. Herein, we present the validation of a new 4-gene signature panel of CDKN1, FDXR, SESN1 and PCNA previously reported to be radiation-responsive genes, using the conventional G2 chromosomal radiosensitivity assay. Radiation-induced G2 chromosomal radiosensitivity at 0.05 Gy and 0.5 Gy IR is presented for a healthy control (n = 45) and a prostate cancer (n = 14) donor cohort. For the prostate cancer cohort, data from two sampling time points (baseline and Androgen Deprivation Therapy (ADT)) is provided, and a significant difference (p > 0.001) between 0.05 Gy and 0.5 Gy was evident for all donor cohorts. Selected donor samples from each cohort also exposed to 0.05 Gy and 0.5 Gy IR were analysed for relative gene expression of the 4-gene signature. In the healthy donor cohort, there was a significant difference in gene expression between IR dose for CDKN1, FXDR and SESN1 but not PCNA and no significant difference found between all prostate cancer donors, unless they were classified as radiation-induced G2 chromosomal radiosensitive. Interestingly, ADT had an effect on radiation response for some donors highlighting intra-individual heterogeneity of prostate cancer donors.
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spelling pubmed-85088812021-10-13 A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity Howe, Orla White, Lisa Cullen, Daniel O’Brien, Grainne Shields, Laura Bryant, Jane Noone, Emma Bradshaw, Shirley Finn, Marie Dunne, Mary Shannon, Aoife M. Armstrong, John McClean, Brendan Meade, Aidan Badie, Christophe Lyng, Fiona M. Int J Mol Sci Article The quest for the discovery and validation of radiosensitivity biomarkers is ongoing and while conventional bioassays are well established as biomarkers, molecular advances have unveiled new emerging biomarkers. Herein, we present the validation of a new 4-gene signature panel of CDKN1, FDXR, SESN1 and PCNA previously reported to be radiation-responsive genes, using the conventional G2 chromosomal radiosensitivity assay. Radiation-induced G2 chromosomal radiosensitivity at 0.05 Gy and 0.5 Gy IR is presented for a healthy control (n = 45) and a prostate cancer (n = 14) donor cohort. For the prostate cancer cohort, data from two sampling time points (baseline and Androgen Deprivation Therapy (ADT)) is provided, and a significant difference (p > 0.001) between 0.05 Gy and 0.5 Gy was evident for all donor cohorts. Selected donor samples from each cohort also exposed to 0.05 Gy and 0.5 Gy IR were analysed for relative gene expression of the 4-gene signature. In the healthy donor cohort, there was a significant difference in gene expression between IR dose for CDKN1, FXDR and SESN1 but not PCNA and no significant difference found between all prostate cancer donors, unless they were classified as radiation-induced G2 chromosomal radiosensitive. Interestingly, ADT had an effect on radiation response for some donors highlighting intra-individual heterogeneity of prostate cancer donors. MDPI 2021-09-30 /pmc/articles/PMC8508881/ /pubmed/34638945 http://dx.doi.org/10.3390/ijms221910607 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Howe, Orla
White, Lisa
Cullen, Daniel
O’Brien, Grainne
Shields, Laura
Bryant, Jane
Noone, Emma
Bradshaw, Shirley
Finn, Marie
Dunne, Mary
Shannon, Aoife M.
Armstrong, John
McClean, Brendan
Meade, Aidan
Badie, Christophe
Lyng, Fiona M.
A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity
title A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity
title_full A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity
title_fullStr A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity
title_full_unstemmed A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity
title_short A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity
title_sort 4-gene signature of cdkn1, fdxr, sesn1 and pcna radiation biomarkers for prediction of patient radiosensitivity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508881/
https://www.ncbi.nlm.nih.gov/pubmed/34638945
http://dx.doi.org/10.3390/ijms221910607
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