Genome wide expression in ADAMTS13-deficient thrombotic thrombocytopenic purpura TTP
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Bart Frank
PROVIDER: E-GEOD-36418 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:This study sought correlates of relapse tendency in TTP by examining gene expression profiles in peripheral blood leukocytes from patients with acquired ADAMTS13-deficient TTP in remission and matched healthy controls for global gene expression and autoantibodies.
2013-03-07 | GSE36418 | GEO
Project description:Background: We aimed to investigate the effects of intravenous immune globulin (IVIG) and rituximab desensitization treatment on kidney transplant rate and blood gene expression profiles by microrarrays. Methods: We enrolled patients with PRA levels >50% and on the deceased-donor waiting list for >5 years. Patients received IVIG (2.0 g/kg) on day 0 and 30; and rituximab (375 mg/m2) on day 15. The antibodies with mean fluorescence intensity (MFI) values > 5,000 were reported to UNET as unacceptable antigens. The gene expression profiles of blood samples collected in PAXGene tube were studied by Affymetrix HuGene 1.0 ST expression arrays. Results: 40 of the 415 patients (10%) on the waiting list were eligible for desensitization treatment and 11 completed the treatment. While 15 of the remaining 29 patients (52%) received a transplant without therapy, only 2 of the 11 desensitized patients (18%) received transplant during a median follow-up of 217 days. While there were no statistically significant difference in demographics, desensitized patients had higher cPRA values (97% vs. 77%, p=0.0005) and more number of unacceptable antigens (39 vs. 10, p=0.0001). There was no significant change in the mean number of unacceptable antigens (39 ± 22 versus 39 ± 23) or reduction in the mean MFI values (11,333 ± 3,133 vs 11,289 ± 3,386). Analysis of genes chosen as significantly differentially expressed revealed downregulation of genes involved in B cells and immune system (CD79a, B and T lymphocyte associated transcript, B cell scaffold protein, CD22, CXCR5, fas apoptotic inhibitory protein). Gene set enrichment analysis using Pathogenesis Based Transcripts created by Edmonton Group demonstrated significant downregulation of B cell associated (p=0.04) and immunoglobulin transcripts (p=0.03). Conclusion: Although, desensitization with IVIG and rituximab decreases the expression of B cell and immunoglobulin associated transcripts, it was not successful in increasing kidney transplant rate or in decreasing the number of unacceptable antigens. Total of 28 arrays included in this study, which corresponding to 9 individuals with paired pre/post treatment samples and an additional 10 untreated control individuals. pair_analysis_normData.txt for paired analysis of pre/post treatment; ordinary_analysis_normData.txt for non-paired analysis include all samples, except for 38 Pax V0 and 56 Pax V1, which shows technicial bias and lowest array quality, hence removed from analysis.
2011-08-29 | E-GEOD-31729 | biostudies-arrayexpress
Project description:Fifth generation Exiqon® locked nucleic acid miRCURY™ LNA microarrays were used to profile the expression of microRNAs in whole blood of patients with non-small cell lung adenocarcinoma and of clinically relevant controls without the disease. Total RNA was isolated from whole blood of 22 cases and 23 controls. Sample RNA was labeled with the Cy3-like Hy3™ dye, mixed with a human universal reference RNA labeled with the Cy5-like Hy5™ dye, and hybridized to two-color miRCURY™ arrays from Exiqon®. - Disease: Lung adenocarcinoma: samples 1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 14, 16, 17, 18, 20, 21, 22, 23, 24, 25 - Disease: No cancer: samples 26, 27, 28, 29, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49
2011-05-20 | E-GEOD-27486 | biostudies-arrayexpress
Project description:Parkinson's disease (PD) progresses relentlessly and affects five million people worldwide. Laboratory tests for PD are critically needed for developing treatments designed to slow or prevent progression of the disease. We performed a transcriptome-wide scan in 105 individuals to interrogate the molecular processes perturbed in cellular blood of patients with early-stage PD. The molecular marker here identified is strongly associated with risk of PD in 66 samples of the training set (third tertile cross-validated odds ratio of 5.7 {P for trend 0.005}). It is further validated in 39 independent test samples (third tertile odds ratio of 5.1 {P for trend 0.04}). The genes differentially expressed in patients with PD, or Alzheimer's or progressive supranuclear palsy offer unique insights into disease-linked processes detectable in peripheral blood. Combining gene expression scans in blood and linked clinical data will facilitate the rapid characterization of candidate biomarkers as demonstrated here with respect to PD. Experiment Overall Design: Whole blood expression data from 50 patients with Parkinson's disease, 33 with neurodegenerative diseases other than PD, and 23 healthy controls.
2008-11-22 | E-GEOD-6613 | biostudies-arrayexpress
Project description:The purpose of this project was to elucidate gene expression in the peripheral whole blood of acute ischemic stroke patients to identify a panel of genes for the diagnosis of acute ischemic stroke. Peripheral blood samples were collected in Paxgene Blood RNA tubes from stroke patients who were >18 years of age with MRI diagnosed ischemic stroke and controls who were non-stroke neurologically healthy. The results suggest a panel of genes can be used to diagnose ischemic stroke, and provide information about the biological pathways involved in the response to acute ischemic stroke in humans. Total RNA extracted from whole blood in n=39 ischemic stroke patients compared to n=24 healthy control subjects.
2010-06-08 | E-GEOD-16561 | biostudies-arrayexpress
Project description:Myc oncoproteins directly regulate transcription by binding to target genes, yet this only explains a fraction of the genes affected by Myc. mRNA turnover is controlled via AU-binding proteins (AUBPs) that recognize AU-rich elements (AREs) found within many transcripts. Analyses of precancerous and malignant Myc-expressing B cells revealed that Myc regulates hundreds of ARE-containing (ARED) genes and select AUBPs. Notably, Myc directly suppresses transcription of Tristetraprolin (TTP/ZFP36), an mRNA-destabilizing AUBP, and this circuit is also operational during B lymphopoiesis and IL7 signaling. Importantly, TTP suppression is a hallmark of cancers with MYC involvement, and restoring TTP impairs Myc-induced lymphomagenesis and abolishes maintenance of the malignant state. Further, there is a selection for TTP loss in malignancy; thus, TTP functions as a tumor suppressor. Finally, Myc/TTP-directed control of select cancer-associated ARED genes is disabled during lymphomagenesis. Thus, Myc targets AUBPs to regulate ARED genes that control tumorigenesis. Ex vivo Eμ-Myc lymphoma cells were infected with MSCV-I-dsRed2 (RFP) and FACS sorted for dsRed2+ cells. These cells were then infected with MSCV-TTP-I-GFP and FACS sorted for GFP expression (TTP-GFP- or TTP-GFP+). These cells were used for subsequent RNA purification, labeling and hybridization to MOE430 2.0 Affymetrix arrays.
2012-08-01 | E-GEOD-37791 | biostudies-arrayexpress
Project description:A total of 38 flash-frozen breast cancer tissues were collected from three medical centers in the Netherlands (i.e. National Cancer institute: n=19; Radboud University Medical Center: n=4; Erasmus University Medical Center: n=15). All tissues were analyzed as laser capture microdissected (LCM) and whole samples (whole tissue lysate: WTL). All gathered samples were primary estrogen receptor (ER) tumors, which were subdivided in two patient groups according to outcome to first line (i.e. recurrent disease setting) tamoxifen therapy based on time-to-progression (TTP): patients which manifested progression of disease before (i.e. TTP <=) 6 months were defined as "poor outcome", while patients which manifested progression after (i.e. TTP>) 6 months were defined as "good outcome". All patients did not receive adjuvant hormonal therapy (i.e. tamoxifen or aromatase inhibitors post-surgical resection of primary tumor). The LCM subset derives from PXD000484 (Erasmus Medical Center samples) and PXD000485 (National Cancer Institute and Radboud University Medical Center).
2016-03-31 | PXD002381 | Pride
Project description:Myc oncoproteins directly regulate transcription by binding to target genes, yet this only explains a fraction of the genes affected by Myc. mRNA turnover is controlled via AU-binding proteins (AUBPs) that recognize AU-rich elements (AREs) found within many transcripts. Analyses of precancerous and malignant Myc-expressing B cells revealed that Myc regulates hundreds of ARE-containing (ARED) genes and select AUBPs. Notably, Myc directly suppresses transcription of Tristetraprolin (TTP/ZFP36), an mRNA-destabilizing AUBP, and this circuit is also operational during B lymphopoiesis and IL7 signaling. Importantly, TTP suppression is a hallmark of cancers with MYC involvement, and restoring TTP impairs Myc-induced lymphomagenesis and abolishes maintenance of the malignant state. Further, there is a selection for TTP loss in malignancy; thus, TTP functions as a tumor suppressor. Finally, Myc/TTP-directed control of select cancer-associated ARED genes is disabled during lymphomagenesis. Thus, Myc targets AUBPs to regulate ARED genes that control tumorigenesis. Wild type, Eµ-TTP-1, precancerous Eμ-Myc and precancerous Eμ-Myc;Eµ-TTP-1 transgenic bone marrow B cells (from 4-6 week old littermates; 94% C57BL/6) were investigated. These samples were used for subsequent RNA purification, labeling and hybridization to MOE430 2.0 Affymetrix arrays.
2012-08-01 | E-GEOD-33474 | biostudies-arrayexpress
Project description:Tristetraprolin (TTP) is an RNA-binding protein that post-transcriptionally suppresses gene expression by delivering mRNA cargo to processing bodies (P-bodies) where the mRNA is degraded. TTP functions as a tumor suppressor in a mouse model of B cell lymphoma, and in some human malignancies low TTP expression correlates with reduced survival. Here we report important prognostic and functional roles for TTP in human prostate cancer. First, gene expression analysis of prostate tumors revealed low TTP expression correlates with patients having high-risk Gleason scores and increased biochemical recurrence. Second, in prostate cancer cells with low levels of endogenous TTP, inducible TTP expression inhibits their growth and proliferation, as well as their clonogenic growth. Third, TTP functions as a tumor suppressor in prostate cancer, as forced TTP expression markedly impairs the tumorigenic potential of prostate cancer cells in a mouse xenograft model. Finally, pathway analysis of gene expression data suggested metabolism is altered by TTP expression in prostate tumor cells, and metabolic analyses revealed that such processes are impaired by TTP, including mitochondrial respiration. Collectively, these findings suggest that TTP is an important prognostic indicator for prostate cancer, and augmenting TTP function would effectively disable the metabolism and proliferation of aggressive prostate tumors.
2016-11-08 | GSE87532 | GEO
Project description:Myc oncoproteins directly regulate transcription by binding to target genes, yet this only explains a fraction of the genes affected by Myc. mRNA turnover is controlled via AU-binding proteins (AUBPs) that recognize AU-rich elements (AREs) found within many transcripts. Analyses of precancerous and malignant Myc-expressing B cells revealed that Myc regulates hundreds of ARE-containing (ARED) genes and select AUBPs. Notably, Myc directly suppresses transcription of Tristetraprolin (TTP/ZFP36), an mRNA-destabilizing AUBP, and this circuit is also operational during B lymphopoiesis and IL7 signaling. Importantly, TTP suppression is a hallmark of cancers with MYC involvement, and restoring TTP impairs Myc-induced lymphomagenesis and abolishes maintenance of the malignant state. Further, there is a selection for TTP loss in malignancy; thus, TTP functions as a tumor suppressor. Finally, Myc/TTP-directed control of select cancer-associated ARED genes is disabled during lymphomagenesis. Thus, Myc targets AUBPs to regulate ARED genes that control tumorigenesis. Lymphomas collected from Eμ-Myc and Eμ-Myc;Eµ-TTP-1 transgenic mice were investigated. These samples were used for subsequent RNA purification, labeling and hybridization to MOE430 2.0 Affymetrix arrays.
2012-08-01 | E-GEOD-37790 | biostudies-arrayexpress