A 4‐gene signature of CDKN1, FDXR, SESN1 and PCNA radiation biomarkers for prediction of patient radiosensitivity

Orla Howe; Lisa White; Daniel Cullen; Grainne O’brien; Laura Shields; Jane Bryant; Emma Noone; Shirley Bradshaw; Marie Finn; Mary Dunne; Aoife M. Shannon; John Armstrong; Brendan McClean; Aidan Meade; Christophe Badie; Fiona M. Lyng

doi:10.3390/ijms221910607

A 4‐gene signature of CDKN1, FDXR, SESN1 and PCNA radiation biomarkers for prediction of patient radiosensitivity

Orla Howe^*, Lisa White, Daniel Cullen, Grainne O’brien, Laura Shields, Jane Bryant, Emma Noone, Shirley Bradshaw, Marie Finn, Mary Dunne, Aoife M. Shannon, John Armstrong, Brendan McClean, Aidan Meade, Christophe Badie, Fiona M. Lyng

^*Corresponding author for this work

Radiation Effects

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Abstract

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 radio-sensitivity 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 high-lighting intra‐individual heterogeneity of prostate cancer donors.

Original language	English
Article number	10607
Journal	International Journal of Molecular Sciences
Volume	22
Issue number	19
DOIs	https://doi.org/10.3390/ijms221910607
Publication status	Published - 30 Sept 2021

Bibliographical note

Funding Information: This research was funded by EU FP7 Network of Excellence DoReMi (Grant Number 249689) and Science Foundation Ireland (11/RFP.1/BMT/3317).

Open Access: 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/).

Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Citation: Howe, O.; White, L.; Cullen, D.; O’Brien, G.; Shields, L.; Bryant, J.; Noone, E.; Bradshaw, S.; Finn, M.; Dunne, M.; et al. A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity. Int. J. Mol. Sci. 2021, 22, 10607.

DOI: https://doi.org/10.3390/ijms221910607

Keywords

Biomarkers
Gene expression
radiosensitivity

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Howe2021A4GeneSignatureOfCDKN1FDXRSESN1AndPCNARadiationBiomarkersIntJMolSciFinal published version, 3.8 MBLicence: CC BY

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Howe, O., White, L., Cullen, D., O’brien, G., Shields, L., Bryant, J., Noone, E., Bradshaw, S., Finn, M., Dunne, M., Shannon, A. M., Armstrong, J., McClean, B., Meade, A., Badie, C., & Lyng, F. M. (2021). A 4‐gene signature of CDKN1, FDXR, SESN1 and PCNA radiation biomarkers for prediction of patient radiosensitivity. International Journal of Molecular Sciences, 22(19), Article 10607. https://doi.org/10.3390/ijms221910607

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title = "A 4‐gene signature of CDKN1, FDXR, SESN1 and PCNA radiation biomarkers for prediction of patient radiosensitivity",

abstract = "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 radio-sensitivity 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 high-lighting intra‐individual heterogeneity of prostate cancer donors.",

keywords = "Biomarkers, Gene expression, radiosensitivity",

author = "Orla Howe and Lisa White and Daniel Cullen and Grainne O{\textquoteright}brien and Laura Shields and Jane Bryant and Emma Noone and Shirley Bradshaw and Marie Finn and Mary Dunne and Shannon, {Aoife M.} and John Armstrong and Brendan McClean and Aidan Meade and Christophe Badie and Lyng, {Fiona M.}",

note = "Funding Information: This research was funded by EU FP7 Network of Excellence DoReMi (Grant Number 249689) and Science Foundation Ireland (11/RFP.1/BMT/3317). Open Access: 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/). Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland. Citation: Howe, O.; White, L.; Cullen, D.; O{\textquoteright}Brien, G.; Shields, L.; Bryant, J.; Noone, E.; Bradshaw, S.; Finn, M.; Dunne, M.; et al. A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity. Int. J. Mol. Sci. 2021, 22, 10607. DOI: https://doi.org/10.3390/ijms221910607",

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Howe, O, White, L, Cullen, D, O’brien, G, Shields, L, Bryant, J, Noone, E, Bradshaw, S, Finn, M, Dunne, M, Shannon, AM, Armstrong, J, McClean, B, Meade, A, Badie, C & Lyng, FM 2021, 'A 4‐gene signature of CDKN1, FDXR, SESN1 and PCNA radiation biomarkers for prediction of patient radiosensitivity', International Journal of Molecular Sciences, vol. 22, no. 19, 10607. https://doi.org/10.3390/ijms221910607

TY - JOUR

T1 - A 4‐gene signature of CDKN1, FDXR, SESN1 and PCNA radiation biomarkers for prediction of patient radiosensitivity

AU - Howe, Orla

AU - White, Lisa

AU - Cullen, Daniel

AU - O’brien, Grainne

AU - Shields, Laura

AU - Bryant, Jane

AU - Noone, Emma

AU - Bradshaw, Shirley

AU - Finn, Marie

AU - Dunne, Mary

AU - Shannon, Aoife M.

AU - Armstrong, John

AU - McClean, Brendan

AU - Meade, Aidan

AU - Badie, Christophe

AU - Lyng, Fiona M.

N1 - Funding Information: This research was funded by EU FP7 Network of Excellence DoReMi (Grant Number 249689) and Science Foundation Ireland (11/RFP.1/BMT/3317). Open Access: 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/). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Citation: Howe, O.; White, L.; Cullen, D.; O’Brien, G.; Shields, L.; Bryant, J.; Noone, E.; Bradshaw, S.; Finn, M.; Dunne, M.; et al. A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity. Int. J. Mol. Sci. 2021, 22, 10607. DOI: https://doi.org/10.3390/ijms221910607

PY - 2021/9/30

Y1 - 2021/9/30

N2 - 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 radio-sensitivity 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 high-lighting intra‐individual heterogeneity of prostate cancer donors.

AB - 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 radio-sensitivity 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 high-lighting intra‐individual heterogeneity of prostate cancer donors.

KW - Biomarkers

KW - Gene expression

KW - radiosensitivity

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U2 - 10.3390/ijms221910607

DO - 10.3390/ijms221910607

M3 - Article

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ER -

A 4‐gene signature of CDKN1, FDXR, SESN1 and PCNA radiation biomarkers for prediction of patient radiosensitivity

Abstract

Bibliographical note

Keywords

UN SDGs

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