Genetic underpinnings of ethnic disparities in bone toxicities between Hispanic and non-Hispanic children treated for acute lymphoblastic leukemia
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PROVIDER: PRJNA685873 | ENA |
REPOSITORIES: ENA
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Project description:Genetic underpinnings of ethnic disparities in bone toxicities between Hispanic and non-Hispanic children treated for acute lymphoblastic leukemia
| PRJNA685874 | ENA
Project description:Background: Colorectal cancer (CRC) remains the second leading cause of cancer mortality in the U.S., with significant racial and ethnic disparities in incidence, survival, and mortality rates. The rising incidence of early-onset CRC and the frequent presentation at advanced stages of CRC among the Hispanics makes this an important ethnic group to study. A deeper understanding of the complex interplay between molecular, genetic, and environmental factors is critical for developing targeted therapies to reduce the prevalence in specific racial and ethnic groups, such as Hispanics. This study explores the role of stress-survival pathway (SSP) genes in early-onset and late-stage CRC, primarily focusing on disparities between Hispanics and Non-Hispanic Whites (NHWs). Additionally, this study investigates the role of MCM10, in contributing to CRC disparities among the Hispanic populations with an emphasis of early-onset and late-stage CRC Hispanics. Methods: One of our previous studies had identified some SSP protein coding genes associated with CRC. The expressions of these genes were validated in CRC cell lines, cDNA arrays, tissue microarrays, and tissue samples using qRT-PCR, and immunohistochemistry. The transcript-level expressions of differentially expressed SSP genes were further evaluated in Hispanic and NHWs tumor tissues, including early onset and late-stage cohorts. Additionally, we performed cellular physiological and functional assays to explore the role of MCM10 in tumor progression, before and after siRNA mediated knockdown. High-throughput transcriptomic and proteomic analyses were performed to reveal the underlying molecular mechanism. Results: We observed differential expressions of twelve SSP genes in CRC cell lines, at the transcript level; that of ten genes in early and late stages using cDNA arrays, and nine genes at the protein levels using tissue microarrays and immunohistochemistry. Hispanic CRC samples showed differential expression of all nine SSP genes compared to NHWs, in early-onset, and late-stage CRC, with all genes being upregulated other than CDK4 and PRDX4 in late-stage CRC and CDK4 in early-onset CRC. Our functional study demonstrated that MCM10 knockdown in CRC cell lines significantly reduced cell proliferation, growth, invasion and migration by inducing cell cycle arrest, apoptosis and reactive oxygen species pathways. The integrative RNA-sequencing and proteomics study reported that the novel gene PPFI1A could be associated with MCM10 mediated cancer progression. The role of MCM10 and PPFI1A in cancer progression has been validated using a Hispanic CRC patient derived organoid. Conclusion: This study highlights the role of SSP genes, particularly MCM10, in colorectal cancer progression and its potential as a biomarker and therapeutic target to address Hispanic CRC disparities.
2025-08-06 | GSE304110 | GEO
Project description:CIDR: Elucidating Epigenetic Mechanisms of Racial/Ethnic Disparities in Pancreatic Cancer
| PRJNA1145494 | ENA
Project description:CIDR: Elucidating Epigenetic Mechanisms of Racial/Ethnic Disparities in Pancreatic Cancer
| PRJNA1145495 | ENA
Project description:Obesity is a major risk factor for several chronic diseases including diabetes, fatty liver disease and cancer. Despite similar propensities for obesity, Hispanics and African Americans exhibit unique and distinct differences in obesity related outcomes such as greater risk of, obesity-related cancers in AA and non alcoholic fatty liver disease (NAFLD) in Hispanics. This study was aimed to determine whether differences in subcutaneous adipose tissue (SAT) gene expression in obese, Hispanic and AA young adults might explain ethnic differences in obesity-related phenotypes. cross-sectional study design to compare subcutaneous adipose tissue gene expression profiles of 19 Hispanic and 17 African American young adults
2011-07-31 | E-GEOD-23506 | biostudies-arrayexpress
Project description:Obesity is a major risk factor for several chronic diseases including diabetes, fatty liver disease and cancer. Despite similar propensities for obesity, Hispanics and African Americans exhibit unique and distinct differences in obesity related outcomes such as greater risk of, obesity-related cancers in AA and non alcoholic fatty liver disease (NAFLD) in Hispanics. This study was aimed to determine whether differences in subcutaneous adipose tissue (SAT) gene expression in obese, Hispanic and AA young adults might explain ethnic differences in obesity-related phenotypes.
2011-08-01 | GSE23506 | GEO
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.
2025-01-01 | GSE242060 | GEO
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.
2025-01-01 | GSE240929 | GEO
Project description:Stress-Survival Pathway Profiling Reveals MCM10 as a Candidate Biomarker of Hispanic Colorectal Cancer Disparities
| PRJNA1298931 | ENA
Project description:SUMMARY Non-Hispanic Black/African American (Black/AA) men in the United States have disproportionally higher incidence and mortality rates of lung cancer compared to non-Hispanic White (NHW) men. Biological factors are believed to play critical roles in driving the disparities. Nevertheless, large-scale genomic studies fail to identify significant somatic differences in lung cancer driver genes contributing to the disparities. Elevated expression of protein arginine methyltransferases (PRMTs) correlating with poorer prognosis is observed in many cancer types. Here, we observed a higher PRMT6 expression in lung cancer of Black/AA men compared to NHW men. PRMT6 formed a heteromer complex with PRMT1 to catalyze arginine methylation of interleukin enhancer-binding factor 2 essential for cell proliferation. Disrupting PRMT1/PRMT6 heteromer complex by a competitive peptide reduced cell proliferation in non-small cell lung cancer cell lines and lung cancer patient-derived organoids. This work implicates that PRMT1/PRMT6 heteromer complex contributes to poorer lung cancer outcomes in Black/AA men vs. NHW men that could serve as a target to eliminate cancer health disparities.
2023-12-15 | MSV000093674 | MassIVE