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: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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Project description:We have identified a specific site in the ERG protein that undergoes post-transcriptional modification. We have mutated this site and generated stably expressing LNCaP cell lines. In this study we evaluated the transcriptional profile induced by ERG in LNCaP stably expressing ERG wild type , ERG mutant or empty vector (EV).
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Project description:Background: Differences in breast cancer outcomes according to race/ethnicity have been reported. Hispanic/Latino (H/L) populations are a genetically admixed and heterogeneous group, with variable fractions of European, Indigenous American and African ancestries. Some studies suggest that breast cancer-specific mortality is higher in U.S. Hispanic/Latinas compared to non-Hispanic Whites (NHW) even after adjustment for socioeconomic status and education. The molecular profile of breast cancer has been widely described in NHWs but equivalent knowledge is lacking in Hispanic/Latinas. We have previously reported that the most prevalent breast cancer intrinsic subtype in Colombian H/L women was Luminal B as defined by surrogate St. Gallen 2013 criteria. In this study we explored ancestry-associated differences in molecular profiles of Luminal B tumors among these highly admixed women. Methods: We performed whole-transcriptome RNA-seq analysis in 42 Luminal tumors (21 Luminal A and 21 Luminal B) from Colombian women. Genetic ancestry was estimated from a panel of 80 ancestry-informative markers (AIM). We categorized patients according to Luminal subtype and to the proportion of European and Indigenous American ancestry and performed differential expression analysis comparing Luminal B against Luminal A tumors according to the assigned ancestry groups. Results: We found 5 genes potentially modulated by genetic ancestry: ERBB2 (Fold Change = 2.367, padj < 0.01), GRB7 (Fold Change = 2.327, padj < 0.01), GSDMB (Fold Change = 1.723, padj < 0.01, MIEN1 (Fold Change = 2.195, padj < 0.01 and ONECUT2 (Fold Change = 2.204, padj < 0.01). In the replication set we found a statistical significant association between European ancestry fraction and the expression levels of ERBB2 (p = 0.02, B = 2.49) and ONECUT2 (p = 0.04, B = -4.87). We also observed statistical significant associations for ERBB2 expression with Indigenous American ancestry (p < 0.001, B = 3.82). This association was not biased by the distribution of HER2+ tumors among the groups analyzed. Conclusions: Our results suggest that genetic ancestry in Hispanic/Latina women might modify ERBB2 gene expression in Luminal tumors. Further analyses are needed to confirm these findings and explore their prognostic value.
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