Stress-Survival Pathway Profiling Reveals MCM10 as a Candidate Biomarker of Hispanic Colorectal Cancer Disparities
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PROVIDER: PRJNA1298931 | ENA |
REPOSITORIES: ENA
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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:Genetic underpinnings of ethnic disparities in bone toxicities between Hispanic and non-Hispanic children treated for acute lymphoblastic leukemia
| PRJNA685874 | ENA
Project description:Genetic underpinnings of ethnic disparities in bone toxicities between Hispanic and non-Hispanic children treated for acute lymphoblastic leukemia
| PRJNA685873 | 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
Project description:Analyzing the US Center for Disease Control’s National Health and Nutrition Examination Survey chemical biomarker data, we identified a suite of toxicants, including metals, pesticides, and personal care product compounds, to which non-Hispanic Black women are disproportionately exposed. To characterize the impact of these toxicants on breast cancer pathways, we performed high throughput transcriptomic analysis of toxicant exposed breast cells.
2024-04-10 | GSE220051 | GEO
Project description:Hispanic Colorectal Cancer Study
| PRJNA339338 | ENA
Project description:Background The role of ERG-status molecular subtyping in prognosis of prostate cancer (PCa) is still under debate. In this study, we identified differentially expressed genes (DEGs) according to ERG-status to explore their enriched pathways and implications in prognosis in Hispanic/Latino PCa patients. Methods RNA from 78 Hispanic PCa tissues from radical prostatectomies (RP) were used for RNA-sequencing. ERGhigh/ERGlow tumor groups were determined based on the 1.5-fold change median expression in non-tumor samples. DEGs with a False Discovery Rate (FDR) < 0.01 and a fold change > 2 were identified between ERGhigh and ERGlow tumors and submitted to enrichment analysis in MetaCore. Survival and association analyses were performed to evaluate biochemical recurrence (BCR)-free survival. Results The identification of 150 DEGs between ERGhigh and ERGlow tumors revealed clustering of most of the non-BCR cases (60%) into de ERGhigh group and most of the BCR cases (60.8%) in ERGlow group. Kaplan-Meier survival curves showed a worst BCR-free survival for ERGlow patients, and a significant reduced risk of BCR was observed for ERGhigh cases (OR = 0.29 (95%CI, 0.10-0.8). Enrichment pathway analysis identified metabolic-related pathways, such as the renin-angiotensin system and angiotensin maturation system, the linoleic acid metabolism, and polyamines metabolism in these ERG groups. Conclusions ERGlow tumor cases were associated with poor BCR-free survival in our Hispanic/Latino patients, with metabolism-related pathways altered in the BCR progression. Impact Our findings suggest the need to dissect the role of diet, metabolism and lifestyle as risk factors for more aggressive PCa subtypes.
2022-10-27 | GSE216490 | GEO
Project description:Hispanic/Latino populations possess a complex genetic structure that reflects recent admixture among and potentially ancient substructure within Native American, European, and West African source populations. Here, we quantify genome-wide patterns of SNP and haplotype variation among 100 individuals with ancestry from Ecuador, Colombia, Puerto Rico, and the Dominican Republic genotyped using Illumina technology. To investigate variations of continental ancestry between different Hispanic/Latino groups (using self-reported country-specific identification of individual, both parents, and all four grandparents) and within them from healthy controls represented in the New York Health Project Biorepository. Genotyped on the Illumina 610-Quad, which is identical to HumanHap550-v3 SNPs plus an additional ~60,000 SNPs for CNV, no CNV data is provided or was analyzed.
2010-04-07 | E-GEOD-21248 | biostudies-arrayexpress
Project description:The risk of atopic dermatitis, hidradenitis suppurativa, lupus erythematosus is significantly higher in African Americans (AA), while White Non-Hispanic (WNH) subjects have a greater risk of psoriasis. The mechanisms underlying disparity in inflammatory skin diseases risks are poorly understood, and the molecular landscape of skin of color including transcriptome and proteome are not well known. To assess whether and how gene expression pattern in normal skin may affect predisposition to specific skin inflammatory diseases, we performed analkysis of gene expression in full thickness skin biopsies obtained from healthy African American and White Non-Hispanic volunteers (all females, aged 22-46).
2024-12-31 | GSE267066 | GEO
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