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Peripheral blood gene expression as a novel genomic biomarker in complicated sarcoidosis

ABSTRACT: Sarcoidosis, a systemic granulomatous syndrome invariably affecting the lung, typically spontaneously remits but in ~20% of cases progresses with severe lung dysfunction or cardiac and neurologic involvement (complicated sarcoidosis). Unfortunately, current biomarkers fail to distinguish patients with remitting (uncomplicated) sarcoidosis from other fibrotic lung disorders, and fail to identify individuals at risk for complicated sarcoidosis. We utilized genome-wide peripheral blood gene expression analysis to identify a gene signature distinguishing sarcoidosis from healthy controls, which also served as a molecular signature for complicated sarcoidosis. Total RNA was isolated from PBMCs using standard molecular biology protocols without DNA contamination or RNA degradation. Sample processing (e.g., cDNA generation, fragmentation, end labeling, hybridization to Affymetrix GeneChip Human Exon 1.0 ST arrays) was performed per manufacturer’s instructions. A total of 29 African descent American (AA) and 10 European descent American (EA) patients with sarcoidosis were included in the overall sarcoidosis cohort with 18 AA and 4 EA patients diagnosed with complicated sarcoidosis.

ORGANISM(S): Homo sapiens

SUBMITTER: Tong Zhou

PROVIDER: E-GEOD-37912 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Peripheral blood gene expression as a novel genomic biomarker in complicated sarcoidosis

Project description:Sarcoidosis, a systemic granulomatous syndrome invariably affecting the lung, typically spontaneously remits but in ~20% of cases progresses with severe lung dysfunction or cardiac and neurologic involvement (complicated sarcoidosis). Unfortunately, current biomarkers fail to distinguish patients with remitting (uncomplicated) sarcoidosis from other fibrotic lung disorders, and fail to identify individuals at risk for complicated sarcoidosis. We utilized genome-wide peripheral blood gene expression analysis to identify a gene signature distinguishing sarcoidosis from healthy controls, which also served as a molecular signature for complicated sarcoidosis.

2012-07-01 | GSE37912 | GEO

MicroRNA expression profiling of the prostate biopsy samples from African American and European American prostate cancer patients

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

Myeloma in African Americans: Myeloma gDNA vs. Control gDNA

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

Gene expression profiling of HPV-negative oropharyngeal cancers and Normal benign uvula, tonsil from European American patients

Project description:Head and neck cancer (HNC) is the fifth most common malignancy worldwide with an annual mortality rate of 200,000. About 90% of HNC can be classified as head and neck squamous cell carcinomas (HNSCC), of which approximately 75% are attributed to alcohol and tobacco consumption and 25 are associated with human papillomavirus (HPV), predominantly HPV16. HPV-associated OPC have better prognosis and a more favorable response to therapy as compared to HPV-negative tumors. Differences in risk factors, age of presentation, clinical behavior and gene expression profiles indicate that HPV-positive and HPV-negative tumors develop via different molecular mechanisms and are biologically distinct. HPV has been characterized as a risk factor for OPC based on race, life style and sexual behavior, impacting survival outcomes for both African American (AA) and European American (EA) patients. According to some reports, the rate of HPV-associated tumors is much lower in AA patients as compared to EA patients in United States. In general, however, AA males have a higher incidence of HNC than any other racial/gender group, and a mortality rate almost three-fold that observed in EA males. Overall, AA patients tend to present with more HPV-negative OPC and have worse prognosis as compared to both HPV-positive and HPV-negative EA patients. This study aimed to compare the gene expression profiles of HPV-negative oropharyngeal squamous cell carcinoma (OPC) and normal benign uvula/tonsil tissues from European American patients and determine what biological processes and pathways are affected in HPV-negative OPCs in EA patients. Additional datasets in this study explore gene expression differences in HNC from EA and AA patients. ANALYSIS 8: Two-condition, one-color experiment: European American (EA) HPV-negative oropharyngeal tumor samples and normal benign uvula/tonsil tissues. Biological replicates: 8 EA HPV active samples and 4 EA Normal samples.

2014-03-05 | E-GEOD-55549 | biostudies-arrayexpress

Label-free global proteome profiling of European American and African American bladder tumor patients.

Project description:Bladder cancer (BLCA) mortality is higher in African American (AA) patients compared to their European American (EA) counterparts, but the molecular mechanism underlying differences are unknown. . Thus, we performed proteomics analysis of AA and EA BLCA and identified higher mitochondrial OXPHOS specifically through complex I activation in AA BLCA.

2024-08-08 | MSV000095559 | MassIVE

Gene expression profiling of the prostate biopsy samples from African American and European American prostate cancer patients

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

Molecular Dissection of Disease Heterogeneity in SLE

Project description:Systemic lupus erythematosus (SLE) affects 1 in 537 of African American (AA) women, which is >2-fold more than European American (EA) women. AA patients also develop the disease at a younger age, have more severe symptoms, and a greater chance of early mortality. We used a multi-omics approach to uncover ancestry-specific immune alterations in SLE patients and healthy controls that may contribute to disease disparities. Cell composition, signaling, and epigenetics were evaluated by mass cytometry; droplet-based single cell transcriptomics and paired proteogenomics (scRNA-Seq/scCITE-Seq). Soluble mediator levels were measured in plasma and stimulated whole blood. TLR3/4/7/8/9 gene expression pathways in B cells and monocytes were enhanced in AA SLE patients compared to EA patients. TLR7/8/9 and IFN phospho-signaling responses were also heightened in healthy AA versus EA controls. Exposure of AA and EA healthy control cells to TLR7/8/9 agonists or IFN resulted in altered immune cell compositions that recapitulated the ancestry-associated differences in SLE patients. These data support that ancestry-based differences in TLR7/8, TLR9, and IFN responses that can be detected in healthy individuals could influence lupus disease course and severity.

2023-10-11 | GSE189050 | GEO

Gene expression profiling of HPV-negative oropharyngeal cancers and Normal benign uvula, tonsil from European American patients

2014-03-05 | GSE55549 | GEO

Gene expression profiling of African American vs European American HPV-negative oropharyngeal squamous cell carcinomas

Project description:Head and neck cancer (HNC) is the fifth most common malignancy worldwide with an annual mortality rate of 200,000. About 90% of HNC can be classified as head and neck squamous cell carcinomas (HNSCC), of which approximately 75% are attributed to alcohol and tobacco consumption and 25% are associated with human papillomavirus (HPV), predominantly HPV16. HPV-associated OPC have better prognosis and a more favorable response to therapy as compared to HPV-negative tumors. Differences in risk factors, age of presentation, clinical behavior and gene expression profiles indicate that HPV-positive and HPV-negative tumors develop via different molecular mechanisms and are biologically distinct. African American (AA) males have a higher incidence of HNC than any other racial/gender group, and a mortality rate almost three-fold that observed in European American (EA) males. Overall, AA patients tend to present with more HPV-negative OPC and have worse prognosis as compared to both HPV-positive and HPV-negative HNSCC in EA patients. Despite the unveiling of differential gene expression patterns, genetic and epigenetic profiles and the compilation of a mutational landscape along with preliminary TCGA data of HPV-related and unrelated HNC, the molecular determinants of the racial disparity in HNC are yet to be identified. This study aimed to compare the gene expression profiles of HPV-negative HNSCC from AA and EA patients, and determine their biological differences. ANALYSIS 2: Two-condition, on-color experiment: African American (AA) vs European American (EA) HPV-negative oropharyngeal squamous cell carcinomas. Biological replicates: 8 African American and 8 European American.

2014-03-05 | E-GEOD-55543 | biostudies-arrayexpress

Fusion Genes in Prostate Cancer: A Comparison in Men of African and European Descent

Project description:Prostate cancer is one of the most prevalent cancers worldwide, particularly affecting men living a western lifestyle and of African descent, suggesting risk factors that are genetic, environmental, and socioeconomic in nature. In the USA, African American (AA) men are disproportionately af-fected, on average suffering from a higher grade of the disease and at a younger age compared to men of European descent (EA). Fusion genes are chimeric products formed by the merging of two separate genes occurring as a result of chromosomal structural changes, for example, inversion or trans/cis-splicing of neighboring genes. They are known drivers of cancer and have been identified in 20% of cancers. Improvements in genomics technologies such as RNA-sequencing coupled with better algorithms for prediction of fusion genes has added to our knowledge of specific gene fu-sions in cancers. At present AA are underrepresented in genomic studies of prostate cancer. The primary goal of this study was to examine molecular differences in predicted fusion genes in a cohort of AA and EA men in the context of prostate cancer using computational approaches. RNA was purified from prostate tissue specimens obtained at surgery from subjects enrolled in the study. Fusion gene predictions were performed using four different fusion gene detection pro-grams. This identified novel putative gene fusions unique to AA and suggested that the fusion gene burden was higher in AA compared to EA men.

2022-04-16 | GSE152929 | GEO

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