Genomic and cellular responses to aspirin treatment in colonic organoids from African- and European-Americans
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE239425 | GEO | 2024/09/01
REPOSITORIES: GEO
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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:Background & Aims: Aspirin (ASA) is a proven chemoprotective agent for colorectal cancer; yet, mechanisms underlying these effects are incompletely understood. Human organoids are an ideal system to study genomic and epigenomic host-environment interactions. Here, we utilize human colonic organoids to profile ASA responses on genome-wide gene expression and chromatin accessibility. Methods: Human colonic organoids from one individual were cultured and treated in triplicate with 3mM ASA or vehicle control (DMSO) for 24 hours. Gene expression and chromatin accessibility were measured using RNA- and ATAC-sequencing, respectively. Differentially expressed genes were analyzed using DESeq2. Gene set enrichment was performed by SetRank. Differentially accessible peaks were analyzed using DiffBind and EdgeR. Motif enrichment was determined using HOMER and diffTF. Results: The results yielded strong transcriptional responses to ASA treatment with significant enrichment for fatty acid oxidation and PPAR signaling in the normal colonic epithelium that were validated in independent organoid lines. A large number of differentially accessible chromatin regions were found in response to ASA treatment with significant enrichment for Fos, Jun and Hnf transcription factor motifs. Integrated analysis of epigenomic and genomic treatment responses highlighted genes and regulatory regions that could mediate ASA’s specific effects in the colon including those involved in chemoprotection and/or toxicity. Conclusions: Assessment of chromatin accessibility and transcriptional responses to ASA yielded new observations about genome-wide effects in the colon facilitated by application of human colonic organoids. This framework can be applied to study colonic ASA responses between individuals and populations in future.
2023-01-01 | GSE198434 | GEO
Project description:Genomic and cellular responses to aspirin treatment in colonic organoids from African- and European-Americans
| PRJNA999280 | ENA
Project description:Epidemiological data have suggested that African Americans (AA) are twice as likely to be diagnosed with multiple myeloma (MM) as compared to European Americans (EA). Here, we have analyzed a set of cytogenetic and genomic data derived from AA and EA MM patients. We have compared the frequency of IgH translocations in a series of data from 115 AA patients from three studies and EA patients from the Eastern Cooperative Oncology Group (ECOG) studies E4A03 and E9487. We have also interrogated tumors from 45 AA and 196 EA MM patients for somatic copy number abnormalities associated with poor outcome. In addition, 35 AA and 178 EA patients were investigated for a transcriptional profile associated with high-risk disease. Overall, based on this cohort, genetic profiles were similar except for a significantly lower frequency of IgH translocations (40% vs. 52%; p=0.032) in AA patients. Frequency differences of somatic copy number aberrations were not significant after correction for multiple testing. There was also no significant difference in the frequency of high-risk disease based upon gene expression profiling. Our study represents the first comprehensive comparisons of the frequency and distribution of molecular alterations in MM tumors between AA and EA patients.
2013-02-25 | GSE44271 | GEO
Project description:Epidemiological data have suggested that African Americans (AA) are twice as likely to be diagnosed with multiple myeloma (MM) as compared to European Americans (EA). Here, we have analyzed a set of cytogenetic and genomic data derived from AA and EA MM patients. We have compared the frequency of IgH translocations in a series of data from 115 AA patients from three studies and EA patients from the Eastern Cooperative Oncology Group (ECOG) studies E4A03 and E9487. We have also interrogated tumors from 45 AA and 196 EA MM patients for somatic copy number abnormalities associated with poor outcome. In addition, 35 AA and 178 EA patients were investigated for a transcriptional profile associated with high-risk disease. Overall, based on this cohort, genetic profiles were similar except for a significantly lower frequency of IgH translocations (40% vs. 52%; p=0.032) in AA patients. Frequency differences of somatic copy number aberrations were not significant after correction for multiple testing. There was also no significant difference in the frequency of high-risk disease based upon gene expression profiling. Our study represents the first comprehensive comparisons of the frequency and distribution of molecular alterations in MM tumors between AA and EA patients. This submission contains 27 of the 45 African American cases analyzed by aCGH. In addition, 196 samples from European American myeloma patients were also analyzed and compared to the 45 African American patients.
2013-02-25 | E-GEOD-44271 | 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 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.
2015-07-27 | GSE64318 | 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.
2015-07-27 | GSE64331 | 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. 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 AA and EA patients. 35 prostate biopsy specimens (tumor and adjacent normal tissues) were collected from 20 African American and 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 (1-way ANOVA) using Partek Genomics Suite program.
2015-07-27 | E-GEOD-64331 | biostudies-arrayexpress