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

Int J Mol Sci. 2021 Sep 30;22(19):10607. doi: 10.3390/ijms221910607.

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 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.

Keywords: biomarkers; gene expression; radiosensitivity.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / pharmacology
  • Androgen Antagonists / therapeutic use
  • Case-Control Studies
  • Chromosomes / radiation effects
  • Cohort Studies
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics*
  • Heat-Shock Proteins / genetics*
  • Humans
  • Male
  • Middle Aged
  • Mitochondrial Proteins / genetics*
  • Multiplex Polymerase Chain Reaction / methods
  • Oxidoreductases Acting on Sulfur Group Donors / genetics*
  • Prognosis
  • Proliferating Cell Nuclear Antigen / genetics*
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / genetics*
  • Radiation Dosage
  • Radiation Tolerance / drug effects
  • Radiation Tolerance / genetics*
  • Real-Time Polymerase Chain Reaction / methods
  • Transcriptome*
  • Young Adult

Substances

  • Androgen Antagonists
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Heat-Shock Proteins
  • Mitochondrial Proteins
  • PCNA protein, human
  • Proliferating Cell Nuclear Antigen
  • SESN1 protein, human
  • Oxidoreductases Acting on Sulfur Group Donors