Abstract 7047: Comparative analysis of transcriptomic and immunological profiles in treatment-naïve black and non-Hispanic White women with high-grade serous ovarian cancer
Authors: Hao Huang, Russel Keathley, Ujin Kim Kim, Horacio Cardenas, Ping Xie, Jianjun Wei, Guangyuan Zhao, Emma L. Barber, Ernst Lengyel, Kenneth P. Nephew, Victoria Bae-Jump, Bin Zhang, Daniela Matei
Journal: Cancer Research (2024)

Abstract Background: Ovarian cancer is a highly lethal gynecological malignancy and high-grade serous histology (HGSOC) accounts for the majority of cases. Platinum-based chemotherapy is the primary treatment. Notably, Black women face the highest mortality-to-incidence ratio across all ethnic groups. This study investigated transcriptomic and immunological differences in tumors from Black compared to NHW women that might explain the poor clinical outcomes observed within this patient cohort. Methods: We collected primary tumor specimens from 36 Black and 31 treatment-naïve NHW patients. After RNA isolation, RNA sequencing (RNA-seq) identified differentially expressed transcripts and Enrichr performed pathway enrichment studies. To confirm the observed gene expression differences, we employed quantitative reverse transcription PCR (qRT-PCR), western blotting, and multiplex immunohistochemistry (mIHC). Additionally, we conducted cell proliferation, colony formation, and cell viability assays to functionally validate potential target genes of interest. Results: Our findings revealed 277 genes with significant differential expression between Black and NHW patients (FDR-adjusted p-value &amp;lt; 0.05). Among these, 103 coding genes were up-regulated, while 81 coding genes were down-regulated in tumors from Black compared to NHW patients. Gene Ontology analyses of these significantly differentially expressed genes highlighted enriched pathways related to DNA damage response, including the insulin receptor (INSR) gene, p53/apoptosis signaling components such as Forkhead box proteins A1 (FOXA1) and FOXB1, as well as genes involved in the cholesterol/lipid modulation pathway, including Low-density lipoprotein (LDL) receptor and Stearoyl-CoA Desaturase (SCD). Notably, silencing INSR and FOXA1 enhanced sensitivity to platinum-based drugs and inhibited cell growth and colony formation. Furthermore, we identified differences in the proportions of key immune cell types between the two patient groups, with tumors from Black patients exhibiting a significantly lower proportion of CD4+ Naïve T-cells and CD4+ regulatory T-cells (Tregs). Conclusions: Overall, our study reveals significant differential gene expression patterns between HGSOC tumors from Black and NHW patients, as well as differences in the proportions of immune cell types. These discoveries provide valuable insights into the biological mechanisms underlying the disparities in outcomes observed between black and NHW patients afflicted with HGSOC. It is critical to further investigate how these biological differences affect clinical outcomes and treatment response in Black women. Citation Format: Hao Huang, Russel Keathley, Ujin Kim Kim, Horacio Cardenas, Ping Xie, Jianjun Wei, Guangyuan Zhao, Emma L. Barber, Ernst Lengyel, Kenneth P. Nephew, Victoria Bae-Jump, Bin Zhang, Daniela Matei. Comparative analysis of transcriptomic and immunological profiles in treatment-naïve black and non-Hispanic White women with high-grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7047.