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Joyce F. Liu, MD, MPH
Joyce F. Liu, MD, MPH
Posted: Friday, February 14, 2025
Distinct molecular and immune features may underlie the elevated mortality-to-incidence ratio observed in Black women with high-grade serous ovarian cancer (HGSOC), according to a study conducted by Daniela Matei, MD, of Northwestern University, Chicago, and colleagues. The study results revealed significant disparities in DNA methylation, transcriptomic profiles, and immune cell infiltration in tumors from Black women compared with White women, which may contribute to less-favorable clinical outcomes. The findings of this study were published in npj Genomic Medicine.
“Our results identify distinct drivers linked to metabolic and oncogenic pathways in HGSOC tumors from Black women that might account for more aggressive biology and decreased response to platinum-based treatment,” stated the study investigators. “Continued efforts to decipher biological determinants of health-care disparities in HGSOC will put forward potential new strategies to tackle the aggressive disease pattern of HGSOC in Black women.”
HGSOC tumor samples were obtained from Black (non-Hispanic Black or African American; n = 35) and White (non-Hispanic White; n = 31) patients; they were analyzed using DNA methylation profiling and RNA sequencing. Immune cell infiltration was assessed via the xCell algorithm and validated with immunohistochemistry. Functional studies involved INSR and FOXA1 knockdown, with analysis of cell proliferation, colony formation, and cisplatin response.
Tumors from Black women showed upregulation of genes involved in DNA damage response, p53 signaling, and lipid metabolism, including INSR and FOXA1, which were associated with increased cell proliferation, colony formation, and cisplatin resistance. Immune profiling revealed significantly lower infiltration of CD4-positive naive and regulatory T cells in tumors from Black patients compared with White patients. HGSOC tumors from White women exhibited a higher density of T-cell subpopulations and stronger expression of immune-related pathways.
Disclosure: The study authors reported no conflicts of interest.
