Methylomic and transcriptomic differences in treatment-naïve profiles among black and non-Hispanic white (NHW) women [RNA-Seq]
Epithelial ovarian cancer (EOC) is a highly lethal gynecological malignancy, with the high-grade serous ovarian cancer subtype (HGSOC) accounting for a significant proportion of cases. Despite platinum-based chemotherapies being the primary treatment for EOC, HGSOC displays high resistance to these therapies. Black women have the highest mortality/incidence ratio of all ethnic groups, and recent studies suggest significant genetic and epigenetic differences between black and non-Hispanic white women who are treatment naïve. This study aims to explore immunogenic differences and hypermethylation phenotype in black women that may contribute to poorer outcomes within this patient group. We collected primary tumor samples from 36 black and 31 non-Hispanic white (NHW) treatment-naïve patients via biopsy and performed methylomic and transcriptomic analyses. Our analysis revealed significant differences in gene expression and methylation between black and NHW patients. Among the differentially expressed genes, we found significant pathway enrichment within p53/apoptosis signaling pathway and cholesterol/lipid modulation. Additionally, we observed mild hypermethylation in black patients vs. the NHW cohort. Furthermore, we discovered differences in the proportion of important immune cell types between the two groups, with CD8+ T-cells and CD4+ memory-resting T-cells being significantly higher proportionally in black patients. In conclusion, our study identified significant differential expression between black and NHW patient groups, as well as mild hypermethylation and differences in the proportion of important immune cell types. These findings provide further insights into the biological mechanisms underlying the disparities in outcomes between black and NHW patients with EOC. Further exploration of the contribution of these differences to clinical outcomes and treatment response in black women is warranted. Overall design: We assessed the transcriptomic and methylomic differences of chemotherapy-resistant HGSOC patient-samples of Black and Non-Hispanic White (NHW) patients using DNA methylation Epic-array and RNA-seq.