S2611
Radiobiology - Translational radiobiology
ESTRO 2026
Poster Discussion 251
Loss of the Y Chromosome and Radiosensitivity: Analysis of clonogenic survival, gene expression, and clinical outcomes across male-origin tumours Vincent Bourbonne 1,2 , Laure Marignol 2 1 Radiation oncology, University Hospital of Brest, Brest, France. 2 Radiation Therapy, Trinity College Dublin, Dublin, Ireland Purpose/Objective: To determine whether loss of the Y chromosome (LOY) influences intrinsic radiosensitivity and clinical outcomes in male-origin cancers by integrating clonogenic survival data, gene expression profiling, and patient survival analyses across multiple tumour types. Material/Methods: Clonogenic survival data (mean surviving fraction at 2 Gy, mSF2) from 125 tumour samples of male origin spanning multiple lineages were extracted from the literature. The dataset was stratified into tumours without LOY and tumours with LOY according to amelogenin profile and karyotypic information available. Mann-Whitney tests were used to compare mSF2 values across LOY subgroups, within individual tumour types and across histologies where sufficient data was available. Correlation of gene expressions (RNASeq) was analyzed between Y chromosome dependent genes, DNA-damage response (DDR) genes, viability and longevity genes and further validated in the Depmap and TCGA pan-cohorts. Survival impact of LOY was evaluated in patients with non-metastasic cancer treated with radiotherapy (TCGA Pan-cancer cohort) using Kaplan-Meier curves and the log-rank test. Results: LOY was identified in 47/125 (37.6%) of tumour samples collated. In this full cohort, LOY status was significantly associated with mSF2 (p < 0.001). Analyses per tumour types showed increased mSF2 values in cell lines with LOY for all histological sub-types except for BLCA (-1.98%) and Ewing sarcoma (-59.3%). Increase in mSF2 varied from 2.74% (ESCC) to +34.96% (LCLC). When the analysis was restricted to tumour types represented by both LOY and no-LOY cell lines (n = 83), LOY status was confirmed to be significantly associated with increased mSF2 (p = 0.003). Expression of Y chromosome dependent genes was significantly correlated with several DDR, viability and longevity genes. Tumour samples with LOY showed a convergent suppression of apoptosis (SMPD1 ↓ , CYFIP2 ↓ ) together with pro-survival epithelial and metabolic programs (CLDN1 ↑ , UMPS ↑ , PPARG/APOC1 ↑ ), which was confirmed in the Depmap and TCGA pan-cohorts. LOY was associated with a significantly lower overall survival (p = 0.008).
Conclusion: Evidence from pooled subsets indicates that LOY may confer radioresistance in specific male-dominant histologies, possibly through diminished apoptotic susceptibility and reinforcement of cellular survival and metabolic maintenance programs. These observations highlight LOY as a potential biomarker for differential radiotherapy response. Validation in larger, clinically annotated cohorts is warranted to assess whether LOY could inform treatment personalization or dose adaptation strategies in radiation oncology. Keywords: Y chromosome, survival outcome, DNA repair
Mini-Oral 570
SCFA-producing gut microbiota associates with favourable chemoradiotherapy response, and SCFAs reduce Tregs and enhance tumour control in vivo Chee Kin Then 1,2 , Reza Hakim 3 , Shing-Chuan Shen 4 , Jo- Ting Tsai 1
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