Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784582202713964544 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8508881 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT howeorla a4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT whitelisa a4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT cullendaniel a4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT obriengrainne a4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT shieldslaura a4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT bryantjane a4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT nooneemma a4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT bradshawshirley a4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT finnmarie a4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT dunnemary a4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT shannonaoifem a4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT armstrongjohn a4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT mccleanbrendan a4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT meadeaidan a4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT badiechristophe a4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT lyngfionam a4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT howeorla 4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT whitelisa 4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT cullendaniel 4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT obriengrainne 4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT shieldslaura 4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT bryantjane 4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT nooneemma 4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT bradshawshirley 4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT finnmarie 4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT dunnemary 4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT shannonaoifem 4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT armstrongjohn 4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT mccleanbrendan 4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT meadeaidan 4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT badiechristophe 4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity AT lyngfionam 4genesignatureofcdkn1fdxrsesn1andpcnaradiationbiomarkersforpredictionofpatientradiosensitivity |