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

被引:5
作者
Howe, Orla [1 ,2 ]
White, Lisa [1 ,2 ]
Cullen, Daniel [2 ,3 ]
O'Brien, Grainne [4 ]
Shields, Laura [5 ]
Bryant, Jane [2 ]
Noone, Emma [6 ]
Bradshaw, Shirley [6 ]
Finn, Marie [6 ]
Dunne, Mary [6 ]
Shannon, Aoife M. [7 ]
Armstrong, John [7 ,8 ]
McClean, Brendan [5 ]
Meade, Aidan [2 ,3 ]
Badie, Christophe [4 ]
Lyng, Fiona M. [2 ,3 ]
机构
[1] Technol Univ Dublin, Sch Biol & Hlth Sci, Dublin D07 XT95, Ireland
[2] Technol Univ Dublin, Radiat & Environm Sci Ctr, FOCAS Res Inst, Dublin D08 CKP1, Ireland
[3] Technol Univ Dublin, Sch Phys & Clin & Optometr Sci, Dublin D07 XT95, Ireland
[4] Publ Hlth England, Radiat Effects Dept, Ctr Radiat Chem & Environm Hazards, Didcot OX11 0RQ, Oxon, England
[5] St Lukes Radiat Oncol Network, Dept Med Phys, Dublin D06 HH36, Ireland
[6] St Lukes Hosp, Clin Trials Unit, St Lukes Radiat Oncol Network, Dublin D06 HH36, Ireland
[7] Canc Trials Ireland, Dublin D11 KXN4, Ireland
[8] St Lukes Hosp, St Lukes Radiat Oncol Network, Dublin D06 HH36, Ireland
基金
爱尔兰科学基金会;
关键词
radiosensitivity; biomarkers; gene expression; G2 CHROMOSOMAL RADIOSENSITIVITY; DOSE HYPER-RADIOSENSITIVITY; BREAST-CANCER PATIENTS; DNA POLYMERASE-DELTA; CELL NUCLEAR ANTIGEN; IONIZING-RADIATION; GENE-EXPRESSION; PROSTATE-CANCER; FILM DOSIMETRY; IDENTIFICATION;
D O I
10.3390/ijms221910607
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
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页数:18
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