Race-specific patterns of epigenetic aging and age-associated differential methylation in normal rectal biopsies: Implications for the biology of aging and its relationship to rectal cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE216024 | GEO | 2022/12/23
REPOSITORIES: GEO
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2012-05-22 | E-GEOD-28000 | biostudies-arrayexpress
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:In the US, the majority of cancer samples analyzed are from white people, leading to biases in racial and ethnic treatment outcomes. Colorectal cancer (CRC) incidence and mortality rates are high in Alabama African Americans (AAs) and Oklahoma American Indians (AIs). We hypothesized that differences between racial groups may partially explain these disparities. Thus, we compared transcriptomic profiles of CRCs of Alabama AAs, Oklahoma AIs, and white people from both states. Compared to CRCs of white people, CRCs of AAs showed (a) higher expression of cytokines and vesicle trafficking toward modulated antitumor-immune activity, and (b) lower expression of the ID1/BMP/SMAD axis, IL22RA1, APOBEC3, and Mucins; and AIs had (c) higher expression of PTGS2/COX2 (an NSAID target/pro-oncogenic inflammation) and splicing regulators, and (d) lower tumor suppressor activities (e.g., TOB2, PCGF2, BAP1). Therefore, targeting strategies designed for white CRC patients may be less effective for AAs/AIs. These findings illustrate needs to develop optimized interventions to overcome racial CRC disparities.
2023-08-23 | GSE237684 | 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
Project description:Prostate cancer (PCa) tends to be more aggressive and lethal in African Americans (AA) compared to European Americans (EA). To further understand the thebiological risk factors associated with PCa disparities observed in AA and EA patients, we performed microRNA profiling using Agilent Human miRNA arrays to identify the differentially expressed microRNAs beween: 1) AA and EA PCa patients; 2) AA PCa vs. AA normal; and 3) EA PCa vs. EA normal.
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Project description:Prostate cancer (PCa) tends to be more aggressive and lethal in African Americans (AA) compared to European Americans (EA). To further understand the biological factors accounting for the PCa disparities observed in AA and EA patients, we performed gene profiling analysis using Affymetrix human exon 1.0 ST arrays to identify the differentially expressed genes in EA PCa vs. EA normal.
2015-08-07 | GSE71783 | GEO
Project description:Prostate cancer (PCa) tends to be more aggressive and lethal in African Americans (AA) compared to European Americans (EA). To further understand the biological factors accounting for the PCa disparities observed in AA and EA patients, we performed gene profiling analysis using Affymetrix human exon 1.0 ST arrays to identify the differentially expressed genes in AA and EA patients.
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Project description:Prostate cancer (PCa) tends to be more aggressive and lethal in African Americans (AA) compared to European Americans (EA). To further understand the thebiological risk factors associated with PCa disparities observed in AA and EA patients, we performed microRNA profiling using Agilent Human miRNA arrays to identify the differentially expressed microRNAs beween: 1) AA and EA PCa patients; 2) AA PCa vs. AA normal; and 3) EA PCa vs. EA normal. 54 prostate biopsy specimens (tumor and adjacent normal tissues) were collected from 14 African American and 13 European American prostate cancer patients. 54 RNA samples, purified from the collected biopy specimens using Qiagen miRNeasy kit, were process and applied to Agilent human miRNA arrays. Array data was normalized and analyzed using Agilent GeneSpring program.
2015-07-27 | E-GEOD-64318 | biostudies-arrayexpress
Project description:Prostate cancer (PCa) tends to be more aggressive and lethal in African Americans (AA) compared to European Americans (EA). To further understand the biological factors accounting for the PCa disparities observed in AA and EA patients, we performed gene profiling analysis using Affymetrix human exon 1.0 ST arrays to identify the differentially expressed genes in EA PCa vs. EA normal. 30 prostate biopsy specimens (tumor and adjacent normal tissues) were collected from 15 European American prostate cancer patients. RNA samples, purified from the collected biopy specimens, were process and applied to Affymetrix human exon ST 1.0 arrays. Array data was normalized, batch-corrected and analyzed (2-way ANOVA) using Partek Genomics Suite program.
2015-08-07 | E-GEOD-71783 | biostudies-arrayexpress