Metabolic pathways enriched according to ERG status are associated with biochemical recurrence in Hispanic/Latino patients with prostate cancer
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ABSTRACT:
PROVIDER: PRJNA893693 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22030000.fastq.gz | Fastqsanger.gz | |||
| SRR22030001.fastq.gz | Fastqsanger.gz | |||
| SRR22030002.fastq.gz | Fastqsanger.gz | |||
| SRR22030003.fastq.gz | Fastqsanger.gz | |||
| SRR22030004.fastq.gz | Fastqsanger.gz |
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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: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.
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Project description:BackgroundThe 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.MethodsRNA 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.ResultsThe 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.ConclusionsERGlow tumor cases were associated with poor BCR-free survival in our Hispanic/Latino patients, with metabolism-related pathways altered in the BCR progression.ImpactOur findings suggest the need to dissect the role of diet, metabolism, and lifestyle as risk factors for more aggressive PCa subtypes.
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Project description:Puerto Rican (PR) Hispanic/Latino (H/L) men are an understudied population that has the highest prostate cancer (PCa) specific mortality among other Hispanic populations. Little information is known about the higher mortality in PR H/L men. It is thought that epigenetic changes in key genes may play a critical role in aggressive tumors. We aimed to identify key 5-hydroxymethylcytosine (5hmC) changes in PR H/L men with aggressive PCa. We performed sequencing analysis using the 5hmC-enriched DNA from 22 prostate tumors and 24 adjacent normal FFPE samples. We identified 808 differentially methylated genes (DMGs) in tumors compared to adjacent normal tissues. These genes suggest key mechanisms, including upregulated signatures of negative Androgen Receptor (AR) regulation, Wnt/β-catenin pathway activation, and downregulation of tumor suppressor genes. Pathway analysis of DMGs demonstrated that DNA repair pathway was most upregulated in tumors. Since 5hmC abundance positively correlates with gene expression levels, we further investigated 808 DMGs in TCGA PCa gene expression data. Further, we identified 59 DMGs with significant gene expression changes in the same direction. Additionally, we identified 111 aggressiveness-related DMGs, of which, two hypomethylated genes (CCDC122, NUDT15) and four hypermethylated genes (PVT1, RPL30, TRMT12, UBR5) were found to be altered at transcriptomic level in a concordant manner in PR H/L PCa patients. Aberrant 5hmC and GE changes in these six genes were also associated with progression-free survival in the mixed PCa population. The 5hmC modifications and associated gene expression changes in these six genes could be linked to the highest prostate cancer (PCa)-specific mortality in PR H/L men. In conclusion, our study identified 59 DMGs showing concordant epigenetic and transcriptomic changes in tumor tissues and 111 DMGs showing association with aggressive PCa among PR H/L men. Our findings have significant implications for understanding these key genes’ molecular mechanisms, which may drive PCa progression and mortality in this population. This will help in developing potential biomarkers or therapeutic targets for personalized treatment strategies in this high-risk subgroup. Future research will explore how these genes contribute to PCa-specific mortality through molecular analyses, with plans to validate them in a larger validation cohort.
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Project description:5hmC-profiles in Puerto Rican Hispanic/Latino men with aggressive prostate cancer
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Project description:We tested the hypothesis that differential gene expression in whole blood will reveal candidate blood biomarkers for exposure to agricultural pesticides and herbicides. Blood gene expression in male Latino farmworkers, where chronic pesticide exposure is occupational, was compared to blood gene expression in age and gender matched Latino manual workers. We identified an expression signature for farmwork, differential expression in genes that correlated with levels of urinary pesticide metabolites, alterations in axonal guidance pathways and statistical models that link farmworker differential expression to Parkinson's disease.
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Project description:Hispanic Colorectal Cancer Study
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Project description:BackgroundHispanics and Latinos are an ethnically heterogeneous population with distinct oral health risk profiles. Few study investigators have examined potential variation in the burden of periodontitis according to Hispanic or Latino background.MethodsThe authors used a multicenter longitudinal population-based cohort study to examine the periodontal health status at screening (2008-2011) of 14,006 Hispanic and Latino adults, aged 18 to 74 years, from four U.S. communities who self-identified as Cuban, Dominican, Mexican, Puerto Rican, Central American or South American. The authors present weighted, age-standardized prevalence estimates and corrected standard errors of probing depth (PD), attachment loss (AL) and periodontitis classified according to the case definition established by the Centers for Disease Control and Prevention and the American Academy of Periodontology (CDC-AAP). The authors used a Wald χ(2) test to compare prevalence estimates across Hispanic or Latino background, age and sex.ResultsFifty-one percent of all participants had exhibited total periodontitis (mild, moderate or severe) per the CDC-AAP classification. Cubans and Central Americans exhibited the highest prevalence of moderate periodontitis (39.9 percent and 37.2 percent, respectively). Across all ages, Mexicans had the highest prevalence of PD across severity thresholds. Among those aged 18 through 44 years, Dominicans consistently had the lowest prevalence of AL at all severity thresholds.ConclusionsMeasures of periodontitis varied significantly by age, sex and Hispanic or Latino background among the four sampled Hispanic Community Health Study/Study of Latinos communities. Further analyses are needed to account for lifestyle, behavioral, demographic and social factors, including those related to acculturation.Practical implicationsAggregating Hispanics and Latinos or using estimates from Mexicans may lead to substantial underestimation or overestimation of the burden of disease, thus leading to errors in the estimation of needed clinical and public health resources. This information will be useful in informing decisions from public health planning to patient-centered risk assessment.
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