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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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/19/10607 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Orla Howe |
| collection | DOAJ |
| 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 (<i>n</i> = 45) and a prostate cancer (<i>n</i> = 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 (<i>p</i> > 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. |
| first_indexed | 2024-03-10T06:58:53Z |
| format | Article |
| id | doaj.art-6c75b40cd28c47d1868693dca6509096 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:58:53Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6c75b40cd28c47d1868693dca65090962023-11-22T16:12:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122191060710.3390/ijms221910607A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient RadiosensitivityOrla Howe0Lisa White1Daniel Cullen2Grainne O’Brien3Laura Shields4Jane Bryant5Emma Noone6Shirley Bradshaw7Marie Finn8Mary Dunne9Aoife M. Shannon10John Armstrong11Brendan McClean12Aidan Meade13Christophe Badie14Fiona M. Lyng15School of Biological & Health Sciences, Technological University Dublin, Grangegorman, D07 XT95 Dublin, IrelandSchool of Biological & Health Sciences, Technological University Dublin, Grangegorman, D07 XT95 Dublin, IrelandRadiation & Environmental Science Centre, FOCAS Research Institute, Technological University Dublin, Camden Row, D08 CKP1 Dublin, IrelandCentre for Radiation, Chemical and Environmental Hazards, Radiation Effects Department, Public Health England, Oxfordshire OX11 0RQ, UKDepartment of Medical Physics, Saint Luke’s Radiation Oncology Network, D06 HH36 Dublin, IrelandRadiation & Environmental Science Centre, FOCAS Research Institute, Technological University Dublin, Camden Row, D08 CKP1 Dublin, IrelandClinical Trials Unit, Saint Luke’s Radiation Oncology Network at St Luke’s Hospital, D06 HH36 Dublin, IrelandClinical Trials Unit, Saint Luke’s Radiation Oncology Network at St Luke’s Hospital, D06 HH36 Dublin, IrelandClinical Trials Unit, Saint Luke’s Radiation Oncology Network at St Luke’s Hospital, D06 HH36 Dublin, IrelandClinical Trials Unit, Saint Luke’s Radiation Oncology Network at St Luke’s Hospital, D06 HH36 Dublin, IrelandCancer Trials Ireland, D11 KXN4 Dublin, IrelandCancer Trials Ireland, D11 KXN4 Dublin, IrelandDepartment of Medical Physics, Saint Luke’s Radiation Oncology Network, D06 HH36 Dublin, IrelandRadiation & Environmental Science Centre, FOCAS Research Institute, Technological University Dublin, Camden Row, D08 CKP1 Dublin, IrelandCentre for Radiation, Chemical and Environmental Hazards, Radiation Effects Department, Public Health England, Oxfordshire OX11 0RQ, UKRadiation & Environmental Science Centre, FOCAS Research Institute, Technological University Dublin, Camden Row, D08 CKP1 Dublin, IrelandThe 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 (<i>n</i> = 45) and a prostate cancer (<i>n</i> = 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 (<i>p</i> > 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.https://www.mdpi.com/1422-0067/22/19/10607radiosensitivitybiomarkersgene expression |
| spellingShingle | 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 A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity International Journal of Molecular Sciences radiosensitivity biomarkers gene expression |
| 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 | radiosensitivity biomarkers gene expression |
| url | https://www.mdpi.com/1422-0067/22/19/10607 |
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