Published December 2, 2024
| Version v1
Journal article
Open
Comparative transcriptomic, epigenomic and immunological analyses identify drivers of disparity in high-grade serous ovarian cancer
Creators
- 1. Northwestern University
- 2. University of Chicago
- 3. Indiana University Bloomington
- 4. Van Andel Institute
- 5. University of North Carolina, Chapel Hill
Description
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.
Data availability
All high-throughput sequencing data and processed data have been deposited in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) data repository: GSEGSE242064. The analyses were performed using publicly available software described in methods.Files
Comparative-transcriptomic-epigenomic-and-immunological-analyses.pdf
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(12.5 MB)
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Additional details
Identifiers
- DOI
- 10.1038/s41525-024-00448-2
- Other
- oai:uchicago.tind.io:14189
Funding
- NCI
- P20 CA233304-01A1