A comprehensive map of alternative polyadenylation in African American and European American lung cancer patients
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE174330 | GEO | 2021/05/13
REPOSITORIES: GEO
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Project description:Deciphering the post-transcriptional mechanisms (PTM) regulating gene expression is critical to understand the dynamics underlying transcriptomic regulation in cancer. Alternative polyadenylation (APA)-regulation of mRNA 3'UTR length by alternating poly(A) site usage-is a key PTM mechanism whose comprehensive analysis in cancer remains an important open challenge. Here we use a method and analysis pipeline that sequences 3'end-enriched RNA directly to overcome the saturation limitation of traditional 5'-3' based sequencing. We comprehensively map the APA landscape in lung cancer in a cohort of 98 tumor/non-involved tissues derived from European American and African American patients. We identify a global shortening of 3'UTR transcripts in lung cancer, with notable functional implications on the expression of both coding and noncoding genes. We find that APA of non-coding RNA transcripts (long non-coding RNAs and microRNAs) is a recurrent event in lung cancer and discover that the selection of alternative polyA sites is a form of non-coding RNA expression control. Our results indicate that mRNA transcripts from EAs are two times more likely than AAs to undergo APA in lung cancer. Taken together, our findings comprehensively map and identify the important functional role of alternative polyadenylation in determining transcriptomic heterogeneity in lung cancer.
| S-EPMC8460807 | biostudies-literature
Project description:A comprehensive map of alternative polyadenylation in African American and European American lung cancer patients
| PRJNA729468 | ENA
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. 126 total samples: 1) 43 white cancer samples; 2) 43 black cancer samples; 3) 27 white control samples; 4) 13 black control samples.
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: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.
2013-01-31 | GSE41967 | 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: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: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
2013-01-31 | GSE41968 | GEO
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)
2013-01-31 | E-GEOD-41967 | biostudies-arrayexpress