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

• Published in: International journal of molecular sciences Vol. 22; no. 19; p. 10607
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.10.2021; MDPI
• Subjects: Bioassays; Biomarkers; Cancer therapies; Cell cycle; Cyclin-dependent kinases; Deprivation; DNA damage; DNA repair; Dosimetry; Gene expression; Heterogeneity; Kinases; Laboratories; Lymphocytes; Patients; Proliferating cell nuclear antigen; Prostate cancer; Radiation effects; Radiation therapy; Radiation tolerance; Radiosensitivity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms221910607

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.