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Molecular Dysregulation Underlying Racial Disparity in Hepatocellular Carcinoma (HCC)

ABSTRACT: Molecular Dysregulation Underlying Racial Disparity in Hepatocellular Carcinoma (HCC)

PROVIDER: PRJNA928394 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23242700.fastq.gz	Fastqsanger.gz
	SRR23242701.fastq.gz	Fastqsanger.gz
	SRR23242702.fastq.gz	Fastqsanger.gz
	SRR23242703.fastq.gz	Fastqsanger.gz
	SRR23242704.fastq.gz	Fastqsanger.gz

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Molecular Dysregulation Underlying Racial Disparity in Hepatocellular Carcinoma (HCC)

Project description:Hepatocellular carcinoma (HCC) is a highly fatal disease with mortality running parallel to its incidence. For HCC patients, there is a statistically significant increase in incidence and mortality and a decrease in 5-year survival rates in African American (AA)/Black patients compared to non-Hispanic (white) patients. There is a gap of knowledge in our understanding of the molecular mechanism underlying the HCC racial disparity between AA/Black and white patients. To address this issue, we analyzed existing RNA-sequencing (RNA-seq) data from HCC patients in the TCGA database, and performed RNA-seq in 14 white and 19 AA/Black HCC patients from Virginia Commonwealth University. In both analysis the only pathway which showed statistically significant activation in AA/Black patients, compared to white patients, was type I interferon (IFN-I) signaling. A four gene signature of IFN-I-stimulated genes (ISGs) showed increased expression in AA/Black HCC tumors compared to their white counterparts. HCC is a disease of chronic inflammation and IFN-I function as a pro-inflammatory and immunosuppressive cytokine. These findings suggest a potential role of IFN-I in conferring disparity in AA/Black HCC patients.

2023-09-15 | GSE223795 | GEO

Integrative analysis of DNA methylation and microRNA expression reveals mechanisms of disparity in hepatocellular carcinoma [miRNA-Seq]

Project description:We evaluate the epigenetic mechanisms of racial disparity in HCC through an integrated analysis of DNA methylation, miRNA, and combined regulation of gene expression. Specifically, we acquired DNA methylation, mRNA-seq, and miRNA-seq data through the analysis of tumor and adjacent normal liver tissues from African Americans (AA) and European Americans (EA) with HCC. Results: Using mixed ANOVA, we identified cytosine-phosphate-guanine (CpG) sites, mRNAs, and miRNAs that are statistically significantly altered in HCC vs. adjacent normal in a race-specific manner. Through integrative analysis, we identified significantly differentially expressed genes in HCC with disparate epigenetic regulation, associated with changes in miRNA expression for AA and DNA methylation for EA.

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Integrative analysis of DNA methylation and microRNA expression reveals mechanisms of disparity in hepatocellular carcinoma [DNA-Methylation]

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Integrative analysis of DNA methylation and microRNA expression reveals mechanisms of disparity in hepatocellular carcinoma [RNA-Seq]

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Transcriptome and DNA Methylome Analyses Reveal Underlying Mechanisms for the Racial Disparity in Uterine Fibroids [RNA-seq]

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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Transcriptome and DNA Methylome Analyses Reveal Underlying Mechanisms for the Racial Disparity in Uterine Fibroids [EPIC Human Methylation Array]

Project description:Genome wide DNA methylation profiling of normal myometrial and fibroid samples. 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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Transcriptome and DNA Methylome Analyses Reveal Underlying Mechanisms for the Racial Disparity in Uterine Fibroids

Project description:Transcriptome and DNA Methylome Analyses Reveal Underlying Mechanisms for the Racial Disparity in Uterine Fibroids

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Dysregulation of Type I Interferon (IFN-I) Signaling: A Potential Contributor to Racial Disparity in Hepatocellular Carcinoma (HCC).

Project description:African-American (AA)/Black hepatocellular carcinoma (HCC) patients have increased incidence and decreased survival rates compared to non-Hispanic (White) patients, the underlying molecular mechanism of which is not clear. Analysis of existing RNA-sequencing (RNA-seq) data in The Cancer Genome Atlas (TCGA) and in-house RNA-sequencing of 14 White and 18 AA/Black HCC patients revealed statistically significant activation of type I interferon (IFN-I) signaling pathway in AA/Black patients. A four-gene signature of IFN-stimulated genes (ISGs) showed increased expression in AA/Black HCC tumors versus White. HCC is a disease of chronic inflammation, and IFN-Is function as pro-inflammatory cytokines. We tested efficacy of ginger extract (GE), a dietary compound known for anti-inflammatory properties, on HCC cell lines derived from White (HepG2), AA/Black (Hep3B and O/20) and Asian (HuH-7) patients. GE exhibited a significantly lower IC50 on Hep3B and O/20 cells than on HepG2 and HuH-7 cells. The GE treatment inhibited the activation of downstream mediators of IFN-I signaling pathways and expression of ISGs in all four HCC cells. Our data suggest that ginger can potentially attenuate IFN-I-mediated signaling pathways in HCC, and cells from AA/Black HCC patients may be more sensitive to ginger. AA/Black HCC patients might benefit from a holistic diet containing ginger.

| S-EPMC10486472 | biostudies-literature

Transcriptome and DNA Methylome Analyses Reveal Underlying Mechanisms for the Racial Disparity in Uterine Fibroids [RNA-seq]

Project description:Transcriptome and DNA Methylome Analyses Reveal Underlying Mechanisms for the Racial Disparity in Uterine Fibroids [RNA-seq]

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Cardiac DNA Methylation Underlies Racial and Socioeconomic Disparities among Patients with End-Stage Heart Failure (RNA-seq)

Project description:African Americans (AA) are 70% more likely than Caucasian Americans (CA) to die from heart failure (HF) even after adjusting for known causes. Although the causal factors responsible for this racial disparity remain unknown, it is theorized that environmental stressors This alarming health disparity represents an important challenge to U.S. healthcare as global prevalence of heart failure has already exceeded epidemic levels with a disease burden that disproportionately impacts members of ethnic and racial minorities. The current multicohort study of cardiac DNA methylation identifies the cardiac epigenome as a previously unrecognized syntax that encodes race-based environmental differences in the failing human heart.

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