P10.17.B Androgen receptor signalling has independent prognostic value and is associated with resistance to temozolomide and tumour growth in glioblastoma

Abstract Background The spectrum of sex differences in glioblastoma (GBM) is a rising topic. GBM more frequent (sex ratio M:F=1.6) and seem to have worse prognosis males (M) compared females. Androgen receptor (AR) expressed but its role biology clinics not yet fully understood. Material Methods We selected from our tumour tissue bank: (i) samples with clinical, pathological molecular annotations (ii) GBM-patient derived cell lines -GBM-PDCL- transcriptomic profiling available parental tumours.AR expression was investigated using multiplex IHC Opal stained-FFPE sections. Sensitivity PDCL hormonotherapy (dihydrotestosterone or enzalutamide EZT) alone combined temozolomide (TMZ) tested WST1 viability assay. Response drugs were correlated AR (high: log2 [FPKM] >2 low: <2). PDCLs dihydrotestosterone secretion examined by ELISA both supernatants lysates. Results In cohort 1188 IDH muted patients, the median follow-up 27.7 (25.8-31.3). M:F 1.68 age at diagnosis 57 years [18-69]. Compared males, females better overall survival 26.1 months vs 20.8 (p<0.0001). multivariate analysis, male gender an independent prognostic factor HR 1.43 CI95%(1.21-1.69) (p<0.0001) adjusted on age, MGMT status Karnofsky indice . Although interaction between significant (p = 0.854), varied through category 1.53 CI95%( 1.01-2.33 ), 1.51 0.888-2.55 ) 1.38 0.857-2.21) for <45 years, 46-55 > 55 respectively. tumours, staining positive 5- 30% cells. After 72h exposure 10nM dihydrotestosterone, ARhigh GBM-PDCLs exhibit nuclear translocation c-myc upregulation, suggesting functional activation receptor. pharmacological blockade increased sensitivity regardless patient’s sex. Moreover, secreted DHT, autocrine paracrine stimulation microenvironment. Conclusion Our study highlights significance where prognosis. GBM-PDCL, we show that androgen vitro associated resistance temozolomide. Further studies are needed investigate