Comparative transcriptomic, epigenomic and immunological analyses identify drivers of disparity in high-grade serous ovarian cancer

比较转录组学、表观基因组学和免疫学分析确定了高级别浆液性卵巢癌差异的驱动因素

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作者:Hao Huang, Russel Keathley, Ujin Kim, Horacio Cardenas, Ping Xie, Jianjun Wei, Ernst Lengyel, Kenneth P Nephew, Guangyuan Zhao, Zhen Fu, Emma L Barber, Masha Kocherginsky, Victoria Bae-Jump, Bin Zhang, Daniela Matei2

Abstract

Black women face the highest mortality-to-incidence ratio from high grade serous ovarian cancer (HGSOC). This study investigated biological differences in HGSOC tumors from Black vs. White women. HGSOC from 35 Black and 31 White patients were analyzed by Infinium Methyation-EPIC array and RNA sequencing. 191 CpG sites were differentially methylated (FDR < 0.05, β value change> 10%) and 277 genes were differentially expressed (FDR < 0.05). Gene Ontology identified enriched pathways related to DNA damage response, p53/apoptosis signaling, and cholesterol/lipid metabolism directly connected with genes like INSR, FOXA1 and FOXB1. INSR and FOXA1 knockdown enhanced cisplatin sensitivity and inhibited cell proliferation and colony formation. Tumors from Black patients were infiltrated by fewer CD4+ naïve and regulatory T-cells. Overall, differences in DNA methylation, transcriptomic profiles and immune cell infiltration were detected in tumors from Black vs. White patients. Further investigation is warranted into how these differences may affect treatment response and outcomes in Black women.

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