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

IF 4.7 2区医学 Q1 GENETICS & HEREDITY

NPJ Genomic Medicine Pub Date : 2024-12-02 DOI:10.1038/s41525-024-00448-2

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 Matei

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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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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。

黑人妇女面临着高级别浆液性卵巢癌（HGSOC）的最高死亡率和发病率。本研究探讨了黑人和白人女性HGSOC肿瘤的生物学差异。采用Infinium甲基化- epic阵列和RNA测序对35例黑人和31例白人患者的HGSOC进行分析。191个CpG位点差异甲基化（FDR为10%），277个基因差异表达（FDR为10%）

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来源期刊

NPJ Genomic Medicine Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

9.40

自引率

1.90%

发文量

审稿时长

17 weeks

期刊介绍： npj Genomic Medicine is an international, peer-reviewed journal dedicated to publishing the most important scientific advances in all aspects of genomics and its application in the practice of medicine. The journal defines genomic medicine as "diagnosis, prognosis, prevention and/or treatment of disease and disorders of the mind and body, using approaches informed or enabled by knowledge of the genome and the molecules it encodes." Relevant and high-impact papers that encompass studies of individuals, families, or populations are considered for publication. An emphasis will include coupling detailed phenotype and genome sequencing information, both enabled by new technologies and informatics, to delineate the underlying aetiology of disease. Clinical recommendations and/or guidelines of how that data should be used in the clinical management of those patients in the study, and others, are also encouraged.