Human metagenome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA637875 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11946812_1.fastq.gz | Fastqsanger.gz | |||
| SRR11946812_2.fastq.gz | Fastqsanger.gz | |||
| SRR11946813_1.fastq.gz | Fastqsanger.gz | |||
| SRR11946813_2.fastq.gz | Fastqsanger.gz | |||
| SRR11946814_1.fastq.gz | Fastqsanger.gz |
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Project description:Epithelial ovarian cancer (EOC) is a highly lethal gynecological malignancy, with the high-grade serous ovarian cancer subtype (HGSOC) accounting for a significant proportion of cases. Despite platinum-based chemotherapies being the primary treatment for EOC, HGSOC displays high resistance to these therapies. Black women have the highest mortality/incidence ratio of all ethnic groups, and recent studies suggest significant genetic and epigenetic differences between black and non-Hispanic white women who are treatment naïve. This study aims to explore immunogenic differences and hypermethylation phenotype in black women that may contribute to poorer outcomes within this patient group. We collected primary tumor samples from 36 black and 31 non-Hispanic white (NHW) treatment-naïve patients via biopsy and performed methylomic and transcriptomic analyses. Our analysis revealed significant differences in gene expression and methylation between black and NHW patients. Among the differentially expressed genes, we found significant pathway enrichment within p53/apoptosis signaling pathway and cholesterol/lipid modulation. Additionally, we observed mild hypermethylation in black patients vs. the NHW cohort. Furthermore, we discovered differences in the proportion of important immune cell types between the two groups, with CD8+ T-cells and CD4+ memory-resting T-cells being significantly higher proportionally in black patients. In conclusion, our study identified significant differential expression between black and NHW patient groups, as well as mild hypermethylation and differences in the proportion of important immune cell types. These findings provide further insights into the biological mechanisms underlying the disparities in outcomes between black and NHW patients with EOC. Further exploration of the contribution of these differences to clinical outcomes and treatment response in black women is warranted.
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Project description:Methylomic and transcriptomic differences in treatment-naïve profiles among black and non-Hispanic white (NHW) women
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Project description:Uterine fibroids (leiomyomas) affect Black women disproportionately in terms of prevalence, incidence, and severity of symptoms. The causes of this racial disparity are essentially unknown. We hypothesized that myometria of Black women are more susceptible to developing fibroids and examined the transcriptomic and DNA methylation profiles of myometria and fibroids from Black and White women for comparison. Myometrial samples cluster by race in both their transcriptome and DNA methylation profiles, whereas fibroid samples only cluster by race in the latter. More differentially expressed genes (DEGs) were detected in the Black and White myometrial comparison than in the fibroid comparison. Leiomyoma gene set expression analysis showed four different clusters of DEGs, including a cluster with highest expression in Black myometrial samples and elevated in all fibroids. One of the DEGs in this group, VWF, was significantly hypomethylated at two CpG probes near a putative enhancer site in Black myometrial and in all fibroid samples compared with White myometrial samples, suggesting that VWF expression is responsive to DNA hypomethylation, a known stress response. These results suggest that the molecular basis for the disparity in fibroid disease between Black and White women could be found in the myometria before fibroid development and not in the fibroids themselves.
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