Expression data from ancestrally diverse group of prostate cancer patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE91037 | GEO | 2016/12/09
SECONDARY ACCESSION(S): PRJNA356726
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:African American (AA) men have a significantly higher mortality rate from prostate cancer (PCa) compared to European American (EA) men. AA men are twice as likely to die from PCa compared to EA men and 8 times as likely as Asian American men to die from PCa. The biological basis for these differences in PCa mortality are unclear. We carried out Copy Number Alteration (CNA) studies on a new set of 40 highly tumor-enriched primary PCas and matched benign prostate tissues from AA men using high resolution Affymetrix 6.0 SNP arrays and expression array analysis using RNAs (GSE71016) from the same tissues using high purity tumors from AA men and matched benign tissue. We have confirmed the specific loss of 4p16.3 described previously and identified a novel tumor suppressor gene, RGS12 at this locus that shows significantly decreased expression in AA PCa but not EA EA PCa.
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Project description:Radical prostatectomy (RP) is a primary treatment option for men with intermediate- and high-risk prostate cancer. Although many are effectively cured with local therapy alone, these men are by definition at higher risk of adverse pathologic features. It has been shown previously that genomic data can be used to predict tumor aggressiveness. Our objective was to evaluate genomic data and it's relationship to pathological stage and grade in a cohort of men that received no treatment other than radical prostatectomy surgery.
2016-05-12 | GSE79957 | GEO
Project description:African-American (AA) men have both a higher incidence and significantly higher mortality rates from prostate cancer (PCa) than European American (EA) men. In this study we have carried out a detailed analysis of both CNAs and gene expression changes in PCas from AA men compared to their matched benign tissues. We have identified MNX1 as a novel androgen regulated oncogene that is upregulated to a greater degree in AA PCa compared to EA PCa. Furthermore, RGS12 is a novel tumor suppressor on 4p16.3 that is preferentially deleted in AA PCa which negatively regulates MNX1 expression.
2016-08-31 | GSE71016 | GEO
Project description:Radical prostatectomy remains one of the more widely-used treatment options for men with prostate cancer. However, few molecular biomarkers have been established to predict patients who are at high risk of biochemical failure. To our knowledge, this is the first such report on miRNA profiling in radical prostatectomy tissue using Nanostring. In addition, this is the first report to look at the prognostic value of miRNAs in the setting of biochemical failure and salvage radiation therapy post-radical prostatectomy.
2015-01-23 | GSE65061 | GEO
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
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Project description:Radical prostatectomy remains one of the more widely-used treatment options for men with prostate cancer. However, few molecular biomarkers have been established to predict patients who are at high risk of biochemical failure. To our knowledge, this is the first such report on miRNA profiling in radical prostatectomy tissue using Nanostring. In addition, this is the first report to look at the prognostic value of miRNAs in the setting of biochemical failure and salvage radiation therapy post-radical prostatectomy. RNA was extracted from tumor-enriched 1mm cores from 43 radical prostatectomy paraffin tissue blocks. 800 miRNAs were profiled using the NanoString nCounter human miRNA assay. mirNAs were then correlated to clinical outcomes.
2015-01-23 | E-GEOD-65061 | biostudies-arrayexpress
Project description:To test the hypothesis that a genomic classifier (GC) would predict biochemical failure (BF) and distant metastasis (DM) in men receiving radiation therapy (RT) after radical prostatectomy (RP).
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Project description:A major challenge in the clinical management of prostate cancer is the inability to definitively diagnose indolent versus aggressive cases. Contributing to this challenge is a lack of basic science understanding of the molecular basis behind aggressiveness subtypes in prostate cancer. DNA methylation is the epigenetic addition of a methyl group to the DNA base cytosine and has been found to regulate cell proliferation and environmental adaptation. We hypothesized that DNA methylation changes are a mechanism by which an aggressive cancer attains phenotypes that distinguish it from indolent cases via disruption of regulatory networks. This hypothesis was tested by comparing DNA methylation between benign prostate and both low grade (Gleason score 6) and high grade (Gleason score 8 to 10) groups. Methylome-wide next generation sequencing was performed on formalin-fixed paraffin embedded (FFPE) samples from radical prostatectomy cases using MBD-isolated genome sequencing (MiGS). This technique uses a DNA methylation binding protein (MBD) to purify fragments from a genomic library with a high level of CpG DNA methylation. These fragments were then sequenced via next generation sequencing, the reads were aligned to a reference genome, and then the reads were counted within non-overlapping 50bp windows genome wide. Statistical analysis was then performed on these windowed counts to produce differentially methylated regions (DMRs). MBD-isolated Genome Sequencing (MiGS) for groups of benign prostate (from cystoprostatectomy), low grade prostate cancer (from radical prostatectomy with Gleason Score 6), and high grade prostate cancer (from radical prostatectomy with Gleason Scores 8 to 10) in both European Americans and African Americans
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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.
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