Comparative transcriptomic, epigenomic and immunological analyses identify drivers of disparity in high-grade serous ovarian cancer
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 R...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-12-01
|
| Series: | npj Genomic Medicine |
| Online Access: | https://doi.org/10.1038/s41525-024-00448-2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850169178123665408 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Hao Huang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-05816bb8f6904172a983bc21bd99b3ec |
| institution | OA Journals |
| issn | 2056-7944 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Genomic Medicine |
| spelling | doaj-art-05816bb8f6904172a983bc21bd99b3ec2025-08-20T02:20:48ZengNature Portfolionpj Genomic Medicine2056-79442024-12-019111310.1038/s41525-024-00448-2Comparative transcriptomic, epigenomic and immunological analyses identify drivers of disparity in high-grade serous ovarian cancerHao Huang0Russel Keathley1Ujin Kim2Horacio Cardenas3Ping Xie4Jianjun Wei5Ernst Lengyel6Kenneth P. Nephew7Guangyuan Zhao8Zhen Fu9Emma L. Barber10Masha Kocherginsky11Victoria Bae-Jump12Bin Zhang13Daniela Matei14Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern UniversityDepartment of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern UniversityDepartment of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern UniversityDepartment of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern UniversityDepartment of Medicine; Hematology/Oncology Division, Feinberg School of Medicine, Northwestern UniversityDepartment of Pathology, Feinberg School of Medicine, Northwestern UniversityDepartment of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of ChicagoSchool of Medicine, Indiana UniversityDepartment of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern UniversityBioinformatics and Biostatistics Core, Van Andel InstituteDepartment of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern UniversityDepartment of Preventive Medicine (Biostatistics), Feinberg School of Medicine, Northwestern UniversityDivision of Gynecologic Oncology, University of North CarolinaDepartment of Medicine; Hematology/Oncology Division, Feinberg School of Medicine, Northwestern UniversityDepartment of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern UniversityAbstract 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.https://doi.org/10.1038/s41525-024-00448-2 |
| spellingShingle | 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 Comparative transcriptomic, epigenomic and immunological analyses identify drivers of disparity in high-grade serous ovarian cancer npj Genomic Medicine |
| title | Comparative transcriptomic, epigenomic and immunological analyses identify drivers of disparity in high-grade serous ovarian cancer |
| title_full | Comparative transcriptomic, epigenomic and immunological analyses identify drivers of disparity in high-grade serous ovarian cancer |
| title_fullStr | Comparative transcriptomic, epigenomic and immunological analyses identify drivers of disparity in high-grade serous ovarian cancer |
| title_full_unstemmed | Comparative transcriptomic, epigenomic and immunological analyses identify drivers of disparity in high-grade serous ovarian cancer |
| title_short | Comparative transcriptomic, epigenomic and immunological analyses identify drivers of disparity in high-grade serous ovarian cancer |
| title_sort | comparative transcriptomic epigenomic and immunological analyses identify drivers of disparity in high grade serous ovarian cancer |
| url | https://doi.org/10.1038/s41525-024-00448-2 |
| work_keys_str_mv | AT haohuang comparativetranscriptomicepigenomicandimmunologicalanalysesidentifydriversofdisparityinhighgradeserousovariancancer AT russelkeathley comparativetranscriptomicepigenomicandimmunologicalanalysesidentifydriversofdisparityinhighgradeserousovariancancer AT ujinkim comparativetranscriptomicepigenomicandimmunologicalanalysesidentifydriversofdisparityinhighgradeserousovariancancer AT horaciocardenas comparativetranscriptomicepigenomicandimmunologicalanalysesidentifydriversofdisparityinhighgradeserousovariancancer AT pingxie comparativetranscriptomicepigenomicandimmunologicalanalysesidentifydriversofdisparityinhighgradeserousovariancancer AT jianjunwei comparativetranscriptomicepigenomicandimmunologicalanalysesidentifydriversofdisparityinhighgradeserousovariancancer AT ernstlengyel comparativetranscriptomicepigenomicandimmunologicalanalysesidentifydriversofdisparityinhighgradeserousovariancancer AT kennethpnephew comparativetranscriptomicepigenomicandimmunologicalanalysesidentifydriversofdisparityinhighgradeserousovariancancer AT guangyuanzhao comparativetranscriptomicepigenomicandimmunologicalanalysesidentifydriversofdisparityinhighgradeserousovariancancer AT zhenfu comparativetranscriptomicepigenomicandimmunologicalanalysesidentifydriversofdisparityinhighgradeserousovariancancer AT emmalbarber comparativetranscriptomicepigenomicandimmunologicalanalysesidentifydriversofdisparityinhighgradeserousovariancancer AT mashakocherginsky comparativetranscriptomicepigenomicandimmunologicalanalysesidentifydriversofdisparityinhighgradeserousovariancancer AT victoriabaejump comparativetranscriptomicepigenomicandimmunologicalanalysesidentifydriversofdisparityinhighgradeserousovariancancer AT binzhang comparativetranscriptomicepigenomicandimmunologicalanalysesidentifydriversofdisparityinhighgradeserousovariancancer AT danielamatei comparativetranscriptomicepigenomicandimmunologicalanalysesidentifydriversofdisparityinhighgradeserousovariancancer |