Integrated genomic and transcriptomic profiling of a breast cancer cohort in the UAE compared with TCGA.

Abstract

e13015 Background: Breast cancer (BC) in the United Arab Emirates (UAE) remains under-characterized relative to large reference cohorts such as The Cancer Genome Atlas (TCGA). We compared UAE BC tumors, including a UAE National subset, with stage-matched TCGA BC to determine whether observed differences reflect TCGA demographic composition or distinct molecular programs with potential therapeutic relevance. Methods: Clinical, genomic, and transcriptomic features were analysed in a UAE BC cohort (n = 83; mutation calls available for 79), comprising UAE Nationals (n = 26) and UAE Non-Nationals (n = 57), against the TCGA BC cohort (n = 99). Sub-analyses compared UAE Nationals with TCGA race-stratified groups: TCGA-White (n = 80) and TCGA-Asian (n = 9). All comparisons were matched by late-stage disease. Tumor mutational burden (TMB) was compared across cohorts. Recurrent protein-altering variants in canonical BC genes were identified. Transcriptomic differences were assessed using gene set variation analysis (GSVA), and tumor microenvironment composition was inferred using xCell 2.0 (adjusted p < 0.05). Results: UAE cohort was younger than TCGA overall (median age 51 vs 55 years; p < 0.05), but this difference was not observed after stratification: UAE Nationals had an intermediate median age (56 years) between TCGA-White (59 years) and TCGA-Asian (52 years). UAE cohort demonstrated higher TMB compared with TCGA (p < 0.0001). Evaluation of recurrent mutations revealed canonical BC driver events predominantly associated with luminal and estrogen receptor–driven biology, including alterations in MAP3K1, PIK3CA, and ARID1A, indicating alignment with established luminal oncogenic pathways. GSVA identified enrichment of extracellular matrix remodeling and innate-immune programs in UAE tumors, including complement, JAK/STAT, and inflammatory signaling gene sets. In contrast, TCGA tumors showed relatively higher estrogen and HER2 response signatures. Immune deconvolution suggested that UAE tumors were relatively enriched for innate and myeloid-associated programs, with increased representation of myeloid cells and Th17- and Th2-associated signals, whereas TCGA tumors showed higher enrichment of adaptive immune components, particularly CD8⁺ T cells. These pathway and immune cell differences persisted when comparing UAE nationals with TCGA-White and TCGA-Asian subsets, with UAE nationals remaining distinct from both TCGA strata. Conclusions: BC in the UAE demonstrate higher reported TMB and a predominantly luminal driver landscape, accompanied by distinct extracellular matrix and innate immune transcriptional programs. These patterns persist in UAE-Nationals relative to TCGA race strata and are not recapitulated within TCGA between White and Asian subgroups, supporting population-associated differences in tumor and microenvironmental biology.