Epigenome-wide association study of Prostate Cancer in African American Men identified differentially methylated genes
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PROVIDER: PRJNA1120800 | ENA |
REPOSITORIES: ENA
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Project description:Men with African ancestry have the highest incidence and mortality rates of prostate cancer (PCa) worldwide. This study aimed to identify differentially methylated genes between tumor vs. adjacent normal and aggressive vs. indolent PCa in 121 African American patients. Epigenome-wide DNA methylation patterns in tumor DNA were assessed using the human Illumina Methylation EPIC V1 array. Around 5,139 differentially methylated CpG-sites (q<0.01, lΔβl>0.2) were identified when comparing normal vs. tumor, with an overall trend of hypermethylation in prostate tumors. Multiple representatives differentially methylated regions (DMRs), including immune-related genes, such as CD40, Galectin3, OX40L, and STING, were detected in prostate tumors when compared to adjacent normal tissues. Based on an epigenetic clock model, we observed that tumors' total number of stem cell divisions and the stem cell division rate were significantly higher than adjacent normal tissues. Regarding aggressiveness, 2,061 differentially methylated CpG-sites (q<0.05, lΔβl>0.05) were identified when the grade group (GG)1 was compared with GG4/5. Among these 2,061 CpG sites, 155 probes were consistently significant in more than one comparison. Among these genes, several immune system genes, such as COL18A1, S100A2, ITGA4, HLA-C, and ADCYAP1, have previously been linked to tumor progression in PCa. Several differentially methylated genes involved in immune-oncologic pathways associated with disease risk or aggressiveness were identified. In addition, 261 African American-specific differentially methylated genes related to the risk of PCa were identified. These results can shed light on potential mechanisms contributing to PCa disparities in the African American population.
2024-08-01 | GSE269244 | 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
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: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 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:Gene expression characteristics of primary prostate cancer tumors from African-Americans are substantially different as compared to European-American men
2021-06-03 | GSE169038 | 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: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.
2018-06-06 | GSE95726 | GEO
Project description:SUMMARY Non-Hispanic Black/African American (Black/AA) men in the United States have disproportionally higher incidence and mortality rates of lung cancer compared to non-Hispanic White (NHW) men. Biological factors are believed to play critical roles in driving the disparities. Nevertheless, large-scale genomic studies fail to identify significant somatic differences in lung cancer driver genes contributing to the disparities. Elevated expression of protein arginine methyltransferases (PRMTs) correlating with poorer prognosis is observed in many cancer types. Here, we observed a higher PRMT6 expression in lung cancer of Black/AA men compared to NHW men. PRMT6 formed a heteromer complex with PRMT1 to catalyze arginine methylation of interleukin enhancer-binding factor 2 essential for cell proliferation. Disrupting PRMT1/PRMT6 heteromer complex by a competitive peptide reduced cell proliferation in non-small cell lung cancer cell lines and lung cancer patient-derived organoids. This work implicates that PRMT1/PRMT6 heteromer complex contributes to poorer lung cancer outcomes in Black/AA men vs. NHW men that could serve as a target to eliminate cancer health disparities.
2023-12-15 | MSV000093674 | MassIVE
Project description:The goal of this clinical trial is to test a new smartphone-based program designed to help African American men get screened for colorectal cancer (CRC). The main question it aims to answer is:
° Are African American men who complete the smartphone-based program more likely to get screened for colorectal cancer than men who do not?
Participants will:
* Complete a baseline survey asking about their colorectal cancer screening history and their thoughts and beliefs about colorectal cancer and the medical system.
* Be randomized to receive the new smartphone-based program or to receive text messages containing colorectal cancer education materials designed by the Centers for Disease Control (CDC). The new program sends text messages with information about colorectal cancer. Some of these text messages have links to videos that try to help men overcome anything that may stand in the way of getting screened.
* Complete a follow-up survey 6 months after the baseline survey. This survey will ask the same questions as the baseline survey.
* A medical records review will be conducted at 6 months to verify whether participants received a colorectal cancer screening test during the study period.
Researchers will compare participants who receive the new smartphone-based program to participants who receive the CDC information. The goal is to see whether the smartphone-based program increasing screening more than standard educational materials available on the internet.
| 106976 | ecrin-mdr-crc