Comparative Analysis of 1,152 African-American and European-American Men with Prostate Cancer Identifies Distinct Genomic and Immunological Differences
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE169038 | GEO | 2021/06/03
REPOSITORIES: GEO
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Project description:The incidence and mortality rates of prostate cancer are significantly higher in African-American men when compared to European-American men. We tested the hypothesis that differences in tumor biology contribute to this survival health disparity. Using microarray technology, we obtained gene expression profiles of primary prostate tumors resected from 33 African-American and 36 European-American patients. These tumors were matched on clinical parameters. We also evaluated 18 non-tumor prostate tissues from 7 African-American and 11 European-American patients. The resulting datasets were analyzed for expression differences on the gene and pathway level comparing African-American with European-American patients. Our analysis revealed a significant number of genes, e.g., 162 transcripts at a false-discovery rate less than 5%, to be differently expressed between African-American and European-American patients. Using a disease association analysis, we identified a common relationship of these transcripts with autoimmunity and inflammation. These findings were corroborated on the pathway level with numerous differently expressed genes clustering in immune response, stress response, cytokine signaling, and chemotaxis pathways. Furthermore, a two-gene tumor signature was identified that accurately differentiated between African-American and European-American patients. This finding was confirmed in a blinded analysis of a second sample set. In conclusion, the gene expression profiles of prostate tumors indicate prominent differences in tumor immunobiology between African-American and European-American men. The profiles portray the existence of a distinct tumor microenvironment in these two patient groups. Experiment Overall Design: A total of 69 fresh-frozen prostate tumors were obtained from the NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) and the Department of Pathology at the University of Maryland (UMD). All tumors were resected adenocarcinomas that had not received any therapy prior to prostatectomy. The macro-dissected CPCTR tumor specimens (n = 59) were reviewed by a CPCTR-associated pathologist, who confirmed the presence of tumor in the specimens. These tissues were collected between 2002 and 2004 at four different sites, with each site providing tissues from both African-American and European-American patients. Information on race/ethnicity (33 African-Americans and 36 European-Americans) was either extracted from medical records (CPCTR) or obtained through an epidemiological questionnaire in which race/ethnicity was self-reported (UMD). Only one patient, a European-American, was also Hispanic. Surrounding non-tumor prostate tissue was collected from 18 of the recruited patients in this study. Of those, 7 were African-American men and 11 were European-American men. We also isolated total RNA from 10 needle biopsy specimens collected from patients at the National Naval Medical Center (one African-American and 9 European-Americans) that did not have prostate cancer. From those, we prepared two RNA pools, each representing 5 patients. Clinicopathological characteristics of the patients, including age at prostatectomy, histology, Gleason score, pathological stage, PSA at diagnosis, tumor size, extraprostatic extension, margin involvement, and seminal vesicle invasion were obtained from CPCTR. For UMD cases, this information was extracted from the medical and pathology records, if available. Written informed consent was obtained from all donors. Tissue collection and study design were approved by the institutional review boards of the participating institutions.
2008-06-15 | E-GEOD-6956 | biostudies-arrayexpress
Project description:The incidence and mortality rates of prostate cancer are significantly higher in African-American men when compared to European-American men. We tested the hypothesis that differences in tumor biology contribute to this survival health disparity. Using microarray technology, we obtained gene expression profiles of primary prostate tumors resected from 33 African-American and 36 European-American patients. These tumors were matched on clinical parameters. We also evaluated 18 non-tumor prostate tissues from 7 African-American and 11 European-American patients. The resulting datasets were analyzed for expression differences on the gene and pathway level comparing African-American with European-American patients. Our analysis revealed a significant number of genes, e.g., 162 transcripts at a false-discovery rate less than 5%, to be differently expressed between African-American and European-American patients. Using a disease association analysis, we identified a common relationship of these transcripts with autoimmunity and inflammation. These findings were corroborated on the pathway level with numerous differently expressed genes clustering in immune response, stress response, cytokine signaling, and chemotaxis pathways. Furthermore, a two-gene tumor signature was identified that accurately differentiated between African-American and European-American patients. This finding was confirmed in a blinded analysis of a second sample set. In conclusion, the gene expression profiles of prostate tumors indicate prominent differences in tumor immunobiology between African-American and European-American men. The profiles portray the existence of a distinct tumor microenvironment in these two patient groups. Keywords: Microdissected tissue analysis
2008-01-01 | GSE6956 | GEO
Project description:African-American (AA) men experience increased risk of developing prostate cancers as well as increased mortality following treatment as compared to European-American (EA) men. The aim of our study was to identify biological factors with potential to predispose AA men to prostate tumor progression and metastasis. High-throughput microarrays were used to investigate differences in global gene expression comparing the two groups.
2009-07-28 | GSE17356 | GEO
Project description:African-American (AA) men experience increased risk of developing prostate cancers as well as increased mortality following treatment as compared to European-American (EA) men. The aim of our study was to identify biological factors with potential to predispose AA men to prostate tumor progression and metastasis. High-throughput microarrays were used to investigate differences in global gene expression comparing the two groups. Experiment Overall Design: To identify cancer-specific gene expression patterns in AA men, we established primary prostate cancer epithelial cells from 14 AA and 13 EA men. Cells were cultured for RNA extraction and hybridization on Affymetrix microarrays.
2009-08-07 | E-GEOD-17356 | 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
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:To investigate genetic and molecular differences that may exist between prostate cancers of African American and European American origin. Gene expression profile analysis was performed comparing RNA seq data of African American prostate cancer cell lines (inhouse) and European American prostate cancer cell lines (public repository)
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Project description:A total of 1,507 probes measured the expression of 517 genes on the custom Illumina DASL assay testing if select genes showed cancer-specific differential expression according to race. Genes were chosen for inclusion in the assay based on existing evidence from the literature and our own data for their importance to prostate cancer, prostate cancer aggressiveness, or cancer in general. 639 FFPE tumor samples (270 African American, 369 European American)
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Project description:In the United States, African-American (AA) women are more likely to develop early-onset breast cancer and have historically poorer outcomes due to this disease compared to European-American (EA) women. Here, we analyzed genomic profiles of breast tumors from young women (<50 years old), matched by tumor subtype, histological grade, and ethnicity (African-American, AA, compared to European-American, EA). DNA copy number alterations (CNAs) were analyzed on the Affymetrix Human SNP Array v 6.0 platform. The study provides insight into the genetic component of ethnicity-related breast cancer health disparities.
2013-01-29 | GSE26232 | GEO
Project description:In the United States, African-American (AA) women are more likely to develop early-onset breast cancer and have historically poorer outcomes due to this disease compared to European-American (EA) women. Here, we analyzed genomic profiles of breast tumors from young women (<50 years old), matched by tumor subtype, histological grade, and ethnicity (African-American, AA, compared to European-American, EA). DNA copy number alterations (CNAs) were analyzed using a 32K BAC tiling path array. The study provides insight into the genetic component of ethnicity-related breast cancer health disparities.
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