Transcriptomic Disparities across Ethnicities: Focused Analysis on Intrinsic Molecular Breast Cancer Subtypes and PRAME Expression

The development and progression of breast cancer is determined by a wide variety of environmental and clinicopathological parameters. Moreover, accumulating evidence suggests that ethnicity might be contributing to cancer risk and treatment response. Technological advancements in the –omics field and big data analyses of breast cancer transcriptomics have made it possible to gain insights into the underlying molecular mechanisms that result in phenotypic disparities observed between patients with different ethnic backgrounds. To date, the majority of transcriptomic studies have focused on breast tumour-derived data from patients of white, black, hispanic and Asian ethnicity. This project aimed to investigate the transcriptomic landscape in breast cancer patients of Arab decent in relation to other ethnic populations. We focused on identifying differential expression of immune gene signatures and of the cancer testis antigen PRAME. For this purpose, we analysed the TCGA breast cancer cohort (n = 993; white, black, hispanic and Asian ethnicity) alongside a local cohort from Qatar (n = 24, Asian and Arab ethnicity). Interestingly, we observed differences in IMS distribution across ethnicities, with an enrichment of basal-like tumour in black and Arab patients, and HER2-enriched tumour in Asian patients. Results have proved that expression of ICR genes is consistent among ethnicities, including RA-QA cohort. However, it has been observed that PD-L1 and IFNG expression is similar in ICR groups of Arab samples; and PD-L1 and PRAME were lower in ICR high Asian samples of RA-QA cohort. Our findings suggest that immune genes expressed in Arab breast cancer reflect unique immunogenic characteristics and survival advantage that should be further investigated and confirmed in a larger cohort.