The role of the ubiquitin ligase UBE4B in neural tumors in adults and children.

• DOI: 10.1200/jco.2024.42.16_suppl.e14034
• Publication Date: 2024-07-03T19:18:55Z
• Authors: Peter E. Zage; Christophe Le Clo...; Tolulope Tosin Ad...; Joanne Xiu; Sonikpreet Aulakh; Emmanuel S. Anton...; Manmeet Singh Ahl...; Theodore Nicolaides; Michael J. Glantz; Matthew James Obe...
• Keywords: 03 medical and health sciences; 0302 clinical medicine

e14034 Background: In cancers of the nervous system such as neuroblastoma (NB), ubiquitin ligase UBE4B directly ubiquitinates growth factor receptors (GFRs), influencing their trafficking and lysosomal degradation. While diverse functions are acknowledged, we hypothesize that expression has distinct associations with outcomes in pediatric versus adult cancers. We examined impact on glioblastoma (GBM) development, growth, metastasis by correlating its patient across age groups. Methods: Glioblastoma samples were IDH1/2 wild type (n = 2072) underwent DNA (592-gene/whole-exome) RNA (whole transcriptome) sequencing at Caris Life Sciences. Samples stratified (transcripts per million – TPM) quartiles for all GBM tumors (Q4: H Q1: L) time tissue collection (younger: < 30 years; older: > 60 years). Cell infiltration tumor microenvironment was inferred quanTIseq. Gene profiles analyzed transcriptomic signature predictive response to immunotherapy. Overall survival (OS) derived from insurance claims data, Kaplan-Meier estimates calculated. Mann-Whitney U Chi-square/Fisher-Exact tests applied appropriate, p-values adjusted multiple comparison. Results: similar between younger 57) older 1115) patients (median: 24.7 vs. 21.6 TPM, p 0.17). patients, those high showed improved OS compared low expressors (24.9 vs 19.2 months [mos]; HR 0.41, 95% CI 0.15 1.11, 0.07). However, not associated among (13.5 12.9 mos; 1.10 0.9 1.3, 0.33). Within cohorts, higher receptor genes observed ( EGFR: 96.57 7.07 0.0092; RET: 0.99 0.30 0.018; NTRK2: 236.9 29.5 0.084). Concurrent mutation PDGFRA also exclusively UBE4B-high (42.9% 0% UBE4B-L, 0.024). Transcriptomic analysis, however, had lower IFN-g scores UBE4B-L (-0.62 -0.41 arbitrary units, 0.02). M1 macrophage cell fractions UBE4B-low 0.33% 3.38%, 0.005), while fraction B cells significantly 9.57% 8.14%, 0.009). Conclusions: Higher cases correlated suggesting it may have utility a prognostic biomarker. Increased GFRs provide rationale new treatment strategies these patients. Future work prioritize designing drug targets UBE4B, offering therapeutic opportunities, especially