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

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

doi:10.1038/s41525-024-00448-2

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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	64
Journal	npj Genomic Medicine
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41525-024-00448-2
State	Published - Dec 2024

Funding

This work was supported by NCI P20 CA233304-01A1 to DM. Tumor specimens were procured through the Lurie Cancer Center Pathology Core supported by NCI CCSG P30 CA060553, NRG Oncology Biospecimen Bank (NCI U24 CA114793 and CA196067), University of Chicago Ovarian Cancer Bank, Melvin and Bren Simon Indiana University Cancer Center Pathology Core and University of North Carolina at Chapel Hill Cancer Center Pathology Core. Sequencing was performed in the NUSeq Core supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. We acknowledge bioinformatics support through the Bioinformatics and Biostatistics Core of Van Andel Institute. This research was supported in part through the computational resources and staff contributions provided for the Quest high-performance computing facility at Northwestern University, which is jointly supported by the Office of the Provost, the Office for Research, and Northwestern University Information Technology.

ASJC Scopus subject areas

Molecular Biology
Genetics
Genetics(clinical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41525-024-00448-2

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Huang, H., Keathley, R., Kim, U., Cardenas, H., Xie, P., Wei, J., Lengyel, E., Nephew, K. P., Zhao, G., Fu, Z., Barber, E. L., Kocherginsky, M., Bae-Jump, V., Zhang, B., & Matei, D. (2024). Comparative transcriptomic, epigenomic and immunological analyses identify drivers of disparity in high-grade serous ovarian cancer. npj Genomic Medicine, 9(1), Article 64. https://doi.org/10.1038/s41525-024-00448-2

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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+ na{\"i}ve 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.",

author = "Hao Huang and Russel Keathley and Ujin Kim and Horacio Cardenas and Ping Xie and Jianjun Wei and Ernst Lengyel and Nephew, {Kenneth P.} and Guangyuan Zhao and Zhen Fu and Barber, {Emma L.} and Masha Kocherginsky and Victoria Bae-Jump and Bin Zhang and Daniela Matei",

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doi = "10.1038/s41525-024-00448-2",

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Huang, H, Keathley, R, Kim, U, Cardenas, H, Xie, P, Wei, J, Lengyel, E, Nephew, KP, Zhao, G, Fu, Z, Barber, EL , Kocherginsky, M, Bae-Jump, V, Zhang, B & Matei, D 2024, 'Comparative transcriptomic, epigenomic and immunological analyses identify drivers of disparity in high-grade serous ovarian cancer', npj Genomic Medicine, vol. 9, no. 1, 64. https://doi.org/10.1038/s41525-024-00448-2

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AU - Huang, Hao

AU - Keathley, Russel

AU - Kim, Ujin

AU - Cardenas, Horacio

AU - Xie, Ping

AU - Wei, Jianjun

AU - Lengyel, Ernst

AU - Nephew, Kenneth P.

AU - Zhao, Guangyuan

AU - Fu, Zhen

AU - Barber, Emma L.

AU - Kocherginsky, Masha

AU - Bae-Jump, Victoria

AU - Zhang, Bin

AU - Matei, Daniela

PY - 2024/12

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N2 - 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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Comparative transcriptomic, epigenomic and immunological analyses identify drivers of disparity in high-grade serous ovarian cancer

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

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