Molecular Disparities in Colorectal Cancers of White Americans, Alabama African Americans, and Oklahoma American Indians
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE237684 | GEO | 2023/08/23
REPOSITORIES: GEO
Similar Datasets
Project description:The incidence and mortality of colorectal cancer (CRC) is higher in African Americans (AAs) than in other ethnic groups in the U. S., but reasons for the disparities are unknown. We performed gene expression profiling and microsatellite instability (MSI) analysis of sporadic CRCs from AAs vs. European Americans (EAs) to assess the contribution to CRC disparities. We evaluated gene expression of 43 AA and 43 EA CRC tumors matched by stage and 40 normal colon tissues using the Agilent human whole genome 4x44K cDNA arrays. Gene and pathway analysis were performed using Significance Analysis of Microarrays (SAM), 10-fold Cross Validation (10-fCV) and Ingenuity Pathway Analysis (IPA). MSI analysis was assessed with five NIH Bethesda markers. SAM revealed that 95 genes were differentially expressed between AA and EA patients at a false discovery rate of <5%. A 10f-CV demonstrated that 9 genes were differentially expressed between AA and EA with an accuracy of 97%. Nine genes (CRYBB2, PSPH, ADAL, VSIG10L, C17orf81, ARSE, ANKRD36B, ZNF835, ARHGAP6) were validated and differential expression confirmed by qRT-PCR in independent test set of 21 patients (10 AA, 11 EA). We also analyzed MSI in 57 of the CRC subjects. Overall, 15.8% of CRC patients had MSI, with a higher rate observed in EA (20%) than in AA (12%). MSI distribution by tumor site was 77% right and 23% left colon. Previously, genetic, epigenetic and environmental factors have been implicated in the etiology of CRC. Our results are the first to implicate differential gene expression in CRC disparities and support the existence of distinct tumor microenvironments in these two patients' populations. 126 total samples: 1) 43 white cancer samples; 2) 43 black cancer samples; 3) 27 white control samples; 4) 13 black control samples.
2012-05-22 | E-GEOD-28000 | biostudies-arrayexpress
Project description:Fecal immunochemical tests (FIT) detecting hemoglobin in stool are widely used for non-invasive colorectal cancer (CRC) screening, but their sensitivity leaves room for improvement. Our aim is to identify novel protein biomarkers in stool that outperform or complement hemoglobin in detecting CRCs and advanced adenomas (AAs). Stool samples (one series of 12 CRCs and 10 controls, and a second series of 81 CRCs, 40 AAs, 43 non-advanced adenomas and 129 controls) were analyzed by mass-spectrometry and searched for human proteins. Classification and regression tree and logistic regression analyses were performed to identify protein combinations that differentiated CRCs and/or AAs from controls. Antibody-based assays for four selected proteins were performed on an independent series of FIT samples (14 CRCs, 16 AAs, 18 non-advanced adenomas and 24 controls) Results: In total, 834 human proteins were identified, of which 29 were significantly enriched in CRCs versus controls in both stool sample series. Combinations of four proteins reached sensitivities of 80% and 45% for detecting CRCs and AAs, at 95% specificity, which was higher than hemoglobin alone.
2020-05-26 | PXD007767 | Pride
Project description:The incidence and mortality of colorectal cancer (CRC) is higher in African Americans (AAs) than in other ethnic groups in the U. S., but reasons for the disparities are unknown. We performed gene expression profiling and microsatellite instability (MSI) analysis of sporadic CRCs from AAs vs. European Americans (EAs) to assess the contribution to CRC disparities. We evaluated gene expression of 43 AA and 43 EA CRC tumors matched by stage and 40 normal colon tissues using the Agilent human whole genome 4x44K cDNA arrays. Gene and pathway analysis were performed using Significance Analysis of Microarrays (SAM), 10-fold Cross Validation (10-fCV) and Ingenuity Pathway Analysis (IPA). MSI analysis was assessed with five NIH Bethesda markers. SAM revealed that 95 genes were differentially expressed between AA and EA patients at a false discovery rate of <5%. A 10f-CV demonstrated that 9 genes were differentially expressed between AA and EA with an accuracy of 97%. Nine genes (CRYBB2, PSPH, ADAL, VSIG10L, C17orf81, ARSE, ANKRD36B, ZNF835, ARHGAP6) were validated and differential expression confirmed by qRT-PCR in independent test set of 21 patients (10 AA, 11 EA). We also analyzed MSI in 57 of the CRC subjects. Overall, 15.8% of CRC patients had MSI, with a higher rate observed in EA (20%) than in AA (12%). MSI distribution by tumor site was 77% right and 23% left colon. Previously, genetic, epigenetic and environmental factors have been implicated in the etiology of CRC. Our results are the first to implicate differential gene expression in CRC disparities and support the existence of distinct tumor microenvironments in these two patients' populations.
2012-05-23 | GSE28000 | GEO
Project description:There are continued disparities in cancer incidence, mortality, and survival between American Indians (AIs) and Whites on cancers responsive to early screening (i.e., breast, colorectal, and cervical) in the US. In New Mexico (NM), AIs compared with other racial/ethnic populations are significantly less likely to adhere to recommended screening guidelines. The purpose of this trial is to develop and pilot test multilevel/multicomponent intervention strategies to enhance screening for breast, colorectal, and cervical cancers.
| 2329355 | ecrin-mdr-crc
Project description:Here, we present the first study showing race and side-specific differences in the trajectories of epigenetic aging in normal colonic mucosa. The cohort conisted of matched biopsies of left/right colon from healthy individuals (n=129). The majority of individuals were African American (n=89). Methylation arrays (Illumina EPIC) were performed on DNA extracted from fresh frozen biopsies taken at the time of colonoscopy. Our results provide novel insight of epigenetic aging underlying racial disparities in CRC. Side-specific colonic epigenetic aging may be a promising marker to guide interventions to reduce CRC burden.
2020-10-16 | GSE151732 | GEO
Project description:In African Americans (AA), the proportion of West African ancestry (WAA) may explain the genetic drivers of health disparities in disease. Analysis of RNA sequencing data from sixty AA-derived primary hepatocytes identified 32 gene expression profiles associated with WAA (FDR <0.05) with enrichment in angiogenesis and inflammatory pathways (FDR <0.1). Association of DNA methylation to WAA identified 1037 differentially methylated regions (FDR <0.05), with hypomethylated genes enriched for drug response pathways. Within the PharmGKB pharmacogene, VDR, PTGIS, ALDH1A1, CYP2C19 and P2RY1 were associated with WAA (p <0.05) with replication of CYP2C19 and VDR in the GTEx liver cohort. For every 1% increment in WAA, P2RY1 gene expression increased by 1.6% and CYP2C19 gene expression decreased by 1.4%, suggesting effects on clopidogrel response and platelet aggregation. We conclude that WAA contributes to variablity in hepatic gene expression and DNA methylation with identified genes indicative of health disparities prevalent in AAs.
2019-10-31 | GSE123995 | GEO
Project description:In African Americans (AA), the proportion of West African ancestry (WAA) may explain the genetic drivers of health disparities in disease. Analysis of RNA sequencing data from sixty AA-derived primary hepatocytes identified 32 gene expression profiles associated with WAA (FDR <0.05) with enrichment in angiogenesis and inflammatory pathways (FDR <0.1). Association of DNA methylation to WAA identified 1037 differentially methylated regions (FDR <0.05), with hypomethylated genes enriched for drug response pathways. Within the PharmGKB pharmacogene, VDR, PTGIS, ALDH1A1, CYP2C19 and P2RY1 were associated with WAA (p <0.05) with replication of CYP2C19 and VDR in the GTEx liver cohort. For every 1% increment in WAA, P2RY1 gene expression increased by 1.6% and CYP2C19 gene expression decreased by 1.4%, suggesting effects on clopidogrel response and platelet aggregation. We conclude that WAA contributes to variablity in hepatic gene expression and DNA methylation with identified genes indicative of health disparities prevalent in AAs.
2023-01-10 | GSE222593 | GEO
Project description:In African Americans (AA), the proportion of West African ancestry (WAA) may explain the genetic drivers of health disparities in disease. Analysis of RNA sequencing data from sixty AA-derived primary hepatocytes identified 32 gene expression profiles associated with WAA (FDR <0.05) with enrichment in angiogenesis and inflammatory pathways (FDR <0.1). Association of DNA methylation to WAA identified 1037 differentially methylated regions (FDR <0.05), with hypomethylated genes enriched for drug response pathways. Within the PharmGKB pharmacogene, VDR, PTGIS, ALDH1A1, CYP2C19 and P2RY1 were associated with WAA (p <0.05) with replication of CYP2C19 and VDR in the GTEx liver cohort. For every 1% increment in WAA, P2RY1 gene expression increased by 1.6% and CYP2C19 gene expression decreased by 1.4%, suggesting effects on clopidogrel response and platelet aggregation. We conclude that WAA contributes to variablity in hepatic gene expression and DNA methylation with identified genes indicative of health disparities prevalent in AAs.
2019-10-31 | GSE124074 | GEO
Project description:Translational Relevance Historically, African Americans have been underrepresented in clinical cancer research. Diversity helps to ensure equal access to new cancer therapies and better treatment for everyone. Cancer research is increasingly focused on classifying patients according to molecular profiles for particular groups. We provide a detailed molecular analysis from paired NSCLC tissues that identified differential coding and noncoding RNA expression in NSCLC from African Americans (AA) and European Americans (EA). Similar to other tumor types, we determined that race-enriched gene and microRNA expression signatures suggest a more aggressive disease in African Americans. Based on predicted drug resistance to adjuvant chemotherapies, AA may not equally benefit from the same range of clinical drugs as EA. Our findings provide a rationale for integrating coding and noncoding transcriptome profiles, along with clinical, demographic, and genomic data, when determining treatment options. Abstract Purpose: To determine if racial differences in gene and microRNA expression translates to differences in lung tumor biology with clinical relevance in African Americans (AA) and European Americans (EA). Experimental Design: The NCI-Maryland Case Control Study includes seven Baltimore City hospitals and is overrepresented with AA patients (~40%). Patients that underwent curative NSCLC surgery between 1998 and 2014 were enrolled. Comparative molecular profiling used mRNA (n = 22 AAs and n = 19 EAs) and microRNA (n = 42 AAs and n = 55 EAs) expression arrays to track differences in paired fresh frozen normal tissues and lung tumor specimens from AA and EA. Pathway enrichment, predicted drug response, tumor microenvironment infiltration, cancer immunotherapy antigen profiling, and microRNA target enrichment were assessed. Results: AA-enriched differential gene expression was characterized by stem-cell and invasion pathways. Differential gene expression in lung tumors from EA were primarily characterized by cell proliferation pathways. Population-specific gene expression was partly driven by population-specific miRNA expression profiles. Drug susceptibility predictions revealed a strong inverse correlation between AA resistance and EA sensitivity to the same panel of drugs. Statistically significant differences in M1 and M2 macrophage infiltration was observed in AA (P <0.05), however, PD-L1, PD-L2 expression was similar between both. Conclusions: Comparative transcriptomic profiling revealed clear differences in lung tumor biology between AA and EA. Increased participation by AA in lung cancer clinical trials are needed to integrate, and leverage, transcriptomic differences with other clinical information to maximize therapeutic benefit in both AA and EA. GSEA, Connectivity Map, CIBERSORT, cancer immunotherapy antigen profiling, and hypergeometric testing for overlapping miRNA targets were performed.
2017-07-28 | GSE101929 | GEO
Project description:Translational Relevance Historically, African Americans have been underrepresented in clinical cancer research. Diversity helps to ensure equal access to new cancer therapies and better treatment for everyone. Cancer research is increasingly focused on classifying patients according to molecular profiles for particular groups. We provide a detailed molecular analysis from paired NSCLC tissues that identified differential coding and noncoding RNA expression in NSCLC from African Americans (AA) and European Americans (EA). Similar to other tumor types, we determined that race-enriched gene and microRNA expression signatures suggest a more aggressive disease in African Americans. Based on predicted drug resistance to adjuvant chemotherapies, AA may not equally benefit from the same range of clinical drugs as EA. Our findings provide a rationale for integrating coding and noncoding transcriptome profiles, along with clinical, demographic, and genomic data, when determining treatment options. Abstract Purpose: To determine if racial differences in gene and microRNA expression translates to differences in lung tumor biology with clinical relevance in African Americans (AA) and European Americans (EA). Experimental Design: The NCI-Maryland Case Control Study includes seven Baltimore City hospitals and is overrepresented with AA patients (~40%). Patients that underwent curative NSCLC surgery between 1998 and 2014 were enrolled. Comparative molecular profiling used mRNA (n = 22 AAs and n = 19 EAs) and microRNA (n = 42 AAs and n = 55 EAs) expression arrays to track differences in paired fresh frozen normal tissues and lung tumor specimens from AA and EA. Pathway enrichment, predicted drug response, tumor microenvironment infiltration, cancer immunotherapy antigen profiling, and microRNA target enrichment were assessed. Results: AA-enriched differential gene expression was characterized by stem-cell and invasion pathways. Differential gene expression in lung tumors from EA were primarily characterized by cell proliferation pathways. Population-specific gene expression was partly driven by population-specific miRNA expression profiles. Drug susceptibility predictions revealed a strong inverse correlation between AA resistance and EA sensitivity to the same panel of drugs. Statistically significant differences in M1 and M2 macrophage infiltration was observed in AA (P <0.05), however, PD-L1, PD-L2 expression was similar between both. Conclusions: Comparative transcriptomic profiling revealed clear differences in lung tumor biology between AA and EA. Increased participation by AA in lung cancer clinical trials are needed to integrate, and leverage, transcriptomic differences with other clinical information to maximize therapeutic benefit in both AA and EA.
2017-08-04 | GSE102286 | GEO