Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA393914 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Understanding the Genetic Risk Underlying Racial Disparities in Uterine Fibroids
| PRJNA393913 | ENA
Project description:Characterization of Plexiform Leiomyomata Provide Further Evidence for Genetic Heterogeneity Underlying Uterine Fibroids
| PRJNA103307 | ENA
Project description:Our study represents a new strategy for identifying drivers and risk factors of uterine fibroids (F) by identifying genes and pathways differentially regulated in myometrial stem cells (SCs) isolated from myometrium without fibroids (MyoN) and from myometrium adjacent to uterine fibroids (MyoF) using RNA-seq approach. Moreover, we will perform the comparison analysis of the transcriptome between MyoF SCs and fibroid SCs to identify differentially expressed genes.
2023-09-24 | GSE158515 | GEO
Project description:Uterine fibroids, or leiomyomas, are noncancerous tumors of the myometrium and the most common reproductive tract tumors in women, with an incidence of up to 80% by age 50. Currently, hysterectomy is the only definitive cure, and effective non-hormonal therapeutics are lacking. Understanding the etiology of fibroids may lead to alternative, less invasive treatments. Several obstetric disorders, including polycystic ovary syndrome (PCOS), have been linked to uterine fibroids, and women with PCOS often exhibit hormonal imbalances, particularly elevated serum testosterone levels. However, the impact of testosterone on the myometrium remains poorly understood. We hypothesize that elevated testosterone may increase the risk of developing uterine fibroids. Using RNA sequencing and MethylationEPIC array analysis, we compared myometrial tissue from women without fibroids (MyoN, n=33), with fibroids (MyoF, n=66), and after testosterone therapy (MyoT, n=7). The transcriptomic and methylation profiles of MyoT clustered with MyoF and were distinct from MyoN. We identified 1,321 differentially expressed protein-coding genes between MyoT and MyoN, while only 494 were found between MyoT and MyoF. Disease ontology analysis of MyoT vs. MyoN revealed enrichment of the fibroid tumor gene set. Fibroid associated genes including TGFβ3, CCND1, SERPINE1, and FGFR1 were upregulated in MyoT and MyoF samples compared to MyoN samples. The DNA methylation profiles of MyoT were closer to those of MyoF, but no correlation was observed between methylation status and gene expression. Our preliminary data suggest that testosterone induces transcriptional and methylation changes in the myometrium consistent with those observed in MyoF tissues. These findings suggest that elevated testosterone may be associated with an increased risk of developing uterine fibroids.
2025-06-01 | GSE296589 | GEO
Project description:Uterine fibroids, or leiomyomas, are noncancerous tumors of the myometrium and the most common reproductive tract tumors in women, with an incidence of up to 80% by age 50. Currently, hysterectomy is the only definitive cure, and effective non-hormonal therapeutics are lacking. Understanding the etiology of fibroids may lead to alternative, less invasive treatments. Several obstetric disorders, including polycystic ovary syndrome (PCOS), have been linked to uterine fibroids, and women with PCOS often exhibit hormonal imbalances, particularly elevated serum testosterone levels. However, the impact of testosterone on the myometrium remains poorly understood. We hypothesize that elevated testosterone may increase the risk of developing uterine fibroids. Using RNA sequencing and MethylationEPIC array analysis, we compared myometrial tissue from women without fibroids (MyoN, n=33), with fibroids (MyoF, n=66), and after testosterone therapy (MyoT, n=7). The transcriptomic and methylation profiles of MyoT clustered with MyoF and were distinct from MyoN. We identified 1,321 differentially expressed protein-coding genes between MyoT and MyoN, while only 494 were found between MyoT and MyoF. Disease ontology analysis of MyoT vs. MyoN revealed enrichment of the fibroid tumor gene set. Fibroid associated genes including TGFβ3, CCND1, SERPINE1, and FGFR1 were upregulated in MyoT and MyoF samples compared to MyoN samples. The DNA methylation profiles of MyoT were closer to those of MyoF, but no correlation was observed between methylation status and gene expression. Our preliminary data suggest that testosterone induces transcriptional and methylation changes in the myometrium consistent with those observed in MyoF tissues. These findings suggest that elevated testosterone may be associated with an increased risk of developing uterine fibroids.
2025-06-01 | GSE288971 | GEO
Project description:Transcriptome and DNA Methylome Analyses Reveal Underlying Mechanisms for the Racial Disparity in Uterine Fibroids
| PRJNA854908 | ENA
Project description:Significant racial disparities exist between Black and White patients with uterine serous carcinoma (USC). While the reasons for these disparities are unclear, but several studies have demonstrated significantly distinct rates of driver mutations between racial groups, including TP53. However, limited research has investigated the transcriptional differences of the tumors between these groups, or the composition of the tumor microenvironment (TME) between these groups. Here, we report the findings from the first single nuclei RNA-sequencing experiment conducted on USC tumors. We find that there are significant differences between the tumors of Black and White patients. Tumors exhibited differential expression of specific genes associated with aggressiveness, such as PAX8, and axon guidance and synaptic signaling pathways in Black and White patients. We also demonstrated that differences in T cell and macrophage populations exist between benign and tumor tissues in the TME of USC, as well as between racial groups. Furthermore, we investigated the connection between PAX8 overexpression and immunosuppression in USC through regulation of several cytokines and chemokines. Notably, we show for the first time that PAX8 activity can influence macrophage gene expression and protein secretion. These studies provide a detailed understanding of USC and a basis for using racial information in USC treatment decisions.
2024-09-13 | GSE260683 | GEO
Project description:Understanding determinants of racial disparities in lung cancer incidence
| PRJNA1165824 | ENA
Project description:Understanding determinants of racial disparities in lung cancer incidence
| PRJNA1165826 | ENA
Project description:<p>Fibroids affect 77% of women by onset of menopause in the U.S. and account for $2.1 billion in healthcare costs each year. Fibroids negatively impact reproductive health causing heavy and painful menses, pelvic pain and pressure, pregnancy complications, and interventions including myomectomy and hysterectomy. Until recently, tumor tissue and cell culture studies investigating fibroid growth have been the primary sources for understanding fibroid pathophysiology. Genetic analysis can provide a powerful and cost effective tool to identify etiological and causal factors, especially since a genetic predisposition to fibroids has already been documented from twin studies. As much as 69% of risk is explained by genetic factors. Racial disparities also support a role for genetics with fibroid risk. African American women have earlier age of onset, more numerous and larger fibroids with a greater lifetime incidence compared to Caucasians. We propose to identify genetic markers for risk of fibroids through a genome-wide association study (GWAS) of African American and Caucasian participants, leveraging ancestral differences to narrow down genomic regions for targeted follow- up analyses. To accomplish this we will take advantage of a unique Vanderbilt resource, the BioVU DNA databank. BioVU currently has over 122,470 adults linked to electronic medical records. From BioVU we have already identified 2,902 African American and Caucasian subjects who meet our stringent inclusion criteria to conduct a GWAS of fibroids, including pelvic imaging. Available imaging is critical, because many women with fibroids are asymptomatic and without imaging, studies may misclassify as many as 51% of women. We have also defined definitive controls who reached menopause without fibroids. We have a strong group of nationally known fibroid researchers who will provide over 10,000 samples for replication. Our first Specific Aim is to conduct a GWAS for association between common single nucleotide polymorphisms (SNPs) and fibroid risk. Using a case-control design we will perform a GWAS in 2,902 (1,451 fibroid cases and 1,451 controls) women from BioVU stratified by African American and Caucasian race. Secondary admixture mapping (AM) analyses will also be performed to identify chromosomal regions of interest to prioritize for replication. Our second Aim is to resequence chromosome regions identified from GWAS and AM to discover rare variants. Finally, in Aim 3 we will replicate SNPs selected from Aim 1 and 2 in independent samples of at least 3,230 fibroid cases and 7,097 controls. We propose an efficient and cost-effective approach to identify genetic risk factors for fibroids, by taking advantage of imaging information and DNA available through BioVU. This study represents the largest GWAS of uterine fibroids and the first among African Americans leveraging emerging technologies and new statistical approaches to conduct this study. Our proposed study will fundamentally change knowledge about fibroids and lay the ground work for breakthroughs in understanding mechanisms of fibroid formation and in identifying novel therapeutic approaches.</p>
| phs001409 | dbGaP