S2621
Radiobiology - Translational radiobiology
ESTRO 2026
1 Institute of Nuclear Technologies for Health (INTECNUS), National Scientific and Technical Research Council (CONICET), Bariloche, Argentina. 2 Division of Cancer Science, The University of Manchester, Manchester, United Kingdom. 3 Institute of Nuclear Technologies for Health (INTECNUS), National Atomic Energy Commission (CNEA), Bariloche, Argentina. 4 Clinical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom. 5 Institute of Nanosciences and Nanotechnology (INN), National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina. 6 Clinical Oncology, Mount Vernon Cancer Centre, Northwood, United Kingdom Purpose/Objective: The peripheral blood leucocyte (PBL) transcriptome has potential for cancer early detection, treatment response, and as a predictive and prognostic biomarker[1-3].Radiotherapy (RT) alters gene expression; however, there are PBL genes modulated by RT which also affect tumour progression and treatment outcome. This study investigated whether radioinduced PBL gene expression changes could be used to create a gene signature (GS) prognostic for tumour response to RT. Material/Methods: Differential gene expression in PBLs from prostate and cervical cancer patients before and during RT (n=4) was assessed using RNAseq (Illumina, 150bp paired- end). Reads were aligned to the hg38 genome with STAR, and the differentially expressed genes (DEGs) analysed using DESeq2. The DEGs were cross-checked in TCGA expression data from prostate (n=494), bladder (n=411), and cervical (n=297) cancer FFPE samples and cell lines. Univariate Cox regression analysis identified DEGs significantly correlated with progression-free survival (PFS). Candidate genes expressed in PBLs, FFPE samples and cell lines were selected to create a GS for each tumour. Multivariate Cox regression established a risk score and classified patients into low- and high-risk groups. Three radiotherapy cohorts [4-6] were used for validation by Kaplan-Meier survival analysis. Data analyses were done with R (v4.2.1). Results: 537 DEGs were identified in PBL at mid-RT, mainly linked to immune response and inflammation (Figure 1). 265 DEGs (49%) were also expressed in prostate, cervical and bladder FFPE tumour samples. DEGs with a significant Hazard Ratio (HR) were identified as candidate prognostic markers. To ensure tumour specificity and avoid genes involved in tumoural infiltration, only those expressed in tumour cell lines (63% prostate, 53.96% bladder and 62.64% cervical ) were selected to create 9-, 20-, 14-GSs, respectively. The GSs were prognostic in TCGA (prostate: n =493, HR=6.51, p<0.0001, bladder: n=149, HR=2.12,
p<0.0001, and cervical: n=294, HR=2.63, p=0.0001) and validated in three independent radiotherapy cohorts (Figure 2).
Figure 1. Volcano plot of differentially expressed genes (|Log2FC|>1, TPM>1, FDR<0.05); top 10 enriched biological processes; and proportion of expressed genes (TPM ≥ 1) in prostate, cervical, and bladder cell lines.
Figure 2. Kaplan–Meier curves showing biochemical recurrence or progression-free survival by high vs low risk score. Conclusion: Radiotherapy modulates the expression of blood leucocyte genes with 49% expressed in cancers and tumour cell lines. Tumour-specific GSs with significant prognostic value were identified and validated. Liquid biopsies during RT reflect treatment outcomes in urogenital and cervical cancers. Larger PBLs cohorts are needed to validate these results. References: [1] Zheng J et al. Ann Transl Med. 2020;8(5):195. doi:10.21037/atm.2020.01.93.[2] Nagumo Y et al. Cancers (Basel). 2022;14(24):6207. doi:10.3390/cancers14246207.[3] Gu L et al. Thorac Cancer. 2018;9(4):431–8. doi:10.1111/1759- 7714.12571.[4] Reardon MD et al. Int J Radiat Oncol Biol Phys. 2025;121(3):752–60. doi:10.1016/j.ijrobp.2024.10.002.[5] Yang L, West CM. Br J Radiol. 2019;92(1093):20180036. doi:10.1259/bjr.20180036.[6] Hoskin P. Bio-CHECC. Univ Manchester; 2020. IRAS 279928; NCT A28707. Keywords: leucocyte transcriptome, biomarker, liquid biopsy.
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