Tubular Transcriptome in the Cprobe Cohort
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE180394 | GEO | 2023/03/09
REPOSITORIES: GEO
Similar Datasets
Project description:We used microarrays to analyze the transcriptome of microdissected renal biopsies from patients with kidney disease and living donors. We derived pathway specific scores for Angiopoietin-Tie signaling pathway activation at mRNA level (or transcriptome level) for individual patients and studied the association of pathway activation with disease outcomes.
2023-03-09 | GSE180393 | GEO
Project description:Angiopoietin-Tie1 signaling is required for lymphatic vascular integrity and both ANGPT2 and TIE1 genetic variants have been associated with lymphedema in patients1, 2. Concurrent with growth-factor signaling, mechanical forces sensed by lymphatic endothelial cells (LECs) are also needed to regulate lymphatics3, 4. How these two pathways might interact in the lymphatic system is unknown. Here, we identified a regulatory network in LECs linking activation of the mechanosensory channel, PIEZO1 to Angiopoietin-Tie signaling and repression of a downstream FOXO1 transcriptional response. RNAseq analysis of dermal LECs from Tie1-deficient embryos showed persistent FOXO1 activity with downregulation of LEC-associated genes including Ccl21a, Foxc2, Gata2 and Gja4, as well as increased expression of the mechanosensory channel, Piezo1. Activation of PIEZO1 in human dermal LECs (HDLECs) by the small molecule agonist, Yoda1, triggered exocytosis of the Tie ligand, Angiopoietin-2 (ANGPT2), activation of Tie/AKT/PI3K signaling and export of FOXO1 out of the nucleus. Our data identify a novel molecular pathway linking mechano-transduction to ANGPT2-Tie1 activity and dynamic modulation of FOXO1 activity needed for patterning and function of the lymphatic system
2024-03-05 | GSE211849 | GEO
Project description:The mechanosensory channel Piezo1 Triggers Angiopoietin-Tie Signaling in the Lymphatics
| PRJNA872364 | ENA
Project description:Genome-wide mRNA expression profiles of 200 primary gastric tumors from the Singapore patient cohort. Gastric cancer (GC) is the second leading cause of global cancer mortality, with individual gastric tumors displaying significant heterogeneity in their deregulation of various oncogenic pathways. We aim to identify major oncogenic pathways in GC that robustly impact patient survival and treatment response. We used an in silico strategy based on gene expression signatures and connectivity analytics to map patterns of oncogenic pathway activation in 25 unique GC cell lines, and in 301 primary gastric cancers from three independent patient cohorts. Of 11 oncogenic pathways previously implicated in GC, we identified three predominant pathways (proliferation/stem cell, NF-kB, and Wnt/b-catenin) deregulated in the majority (>70%) of gastric tumors. Using a variety of proliferative, Wnt, and NF-kB-related assays, we experimentally validated the pathway predictions in multiple GC cell lines showing similar pathway activation patterns in vitro. Patients stratified at the level of individual pathways did not exhibit consistent differences in clinical outcome. However, patients grouped by oncogenic pathway combinations demonstrated robust and significant survival differences (e.g., high proliferation/high NF-kB vs. low proliferation/low NF-kB), suggesting that tumor behavior in GC is likely influenced by the combined effects of multiple oncogenic pathways. Our results demonstrate that GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Keywords: gastric cancer, primary tumor
2009-10-06 | GSE15459 | GEO
Project description:Sepsis remains a lethal ailment with imprecise treatment and ill-understood biology. A clinical transcriptomic analysis of sepsis patients was performed for the first time in India and revealed large-scale change in blood gene expression in patients of severe sepsis and septic shock admitted to ICU. Three biological processes were quantified using scores derived from the corresponding transcriptional modules. Comparison of the module scores revealed that genes associated with immune response were more suppressed compared to the inflammation-associated genes. These findings will have great implication in the treatment and prognosis of severe sepsis/septic shock if translated into a bedside tool.
2022-09-12 | GSE137340 | GEO
Project description:Genome-wide mRNA expression profiles of 31 primary gastric tumors from the UK patient cohort. Gastric cancer (GC) is the second leading cause of global cancer mortality, with individual gastric tumors displaying significant heterogeneity in their deregulation of various oncogenic pathways. We aim to identify major oncogenic pathways in GC that robustly impact patient survival and treatment response. We used an in silico strategy based on gene expression signatures and connectivity analytics to map patterns of oncogenic pathway activation in 25 unique GC cell lines, and in 301 primary gastric cancers from three independent patient cohorts. Of 11 oncogenic pathways previously implicated in GC, we identified three predominant pathways (proliferation/stem cell, NF-kB, and Wnt/b-catenin) deregulated in the majority (>70%) of gastric tumors. Using a variety of proliferative, Wnt, and NF-kB-related assays, we experimentally validated the pathway predictions in multiple GC cell lines showing similar pathway activation patterns in vitro. Patients stratified at the level of individual pathways did not exhibit consistent differences in clinical outcome. However, patients grouped by oncogenic pathway combinations demonstrated robust and significant survival differences (e.g., high proliferation/high NF-kB vs. low proliferation/low NF-kB), suggesting that tumor behavior in GC is likely influenced by the combined effects of multiple oncogenic pathways. Our results demonstrate that GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Keywords: gastric cancer, cell culture
2009-10-06 | GSE15456 | GEO
Project description:Genome-wide mRNA expression profiles of 200 primary gastric tumors from the Singapore patient cohort. Gastric cancer (GC) is the second leading cause of global cancer mortality, with individual gastric tumors displaying significant heterogeneity in their deregulation of various oncogenic pathways. We aim to identify major oncogenic pathways in GC that robustly impact patient survival and treatment response. We used an in silico strategy based on gene expression signatures and connectivity analytics to map patterns of oncogenic pathway activation in 25 unique GC cell lines, and in 301 primary gastric cancers from three independent patient cohorts. Of 11 oncogenic pathways previously implicated in GC, we identified three predominant pathways (proliferation/stem cell, NF-kB, and Wnt/b-catenin) deregulated in the majority (>70%) of gastric tumors. Using a variety of proliferative, Wnt, and NF-kB-related assays, we experimentally validated the pathway predictions in multiple GC cell lines showing similar pathway activation patterns in vitro. Patients stratified at the level of individual pathways did not exhibit consistent differences in clinical outcome. However, patients grouped by oncogenic pathway combinations demonstrated robust and significant survival differences (e.g., high proliferation/high NF-kB vs. low proliferation/low NF-kB), suggesting that tumor behavior in GC is likely influenced by the combined effects of multiple oncogenic pathways. Our results demonstrate that GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Experiment Overall Design: Profiling of 200 primary gastric tumors on Affymetrix GeneChip Human Genome U133 Plus 2.0 Array. All tumors were collected with approvals from the National Cancer Centre, Singapore; the Research Ethics Review Committee; and signed patient informed consent.
2009-04-10 | E-GEOD-15459 | biostudies-arrayexpress
Project description:Genome-wide mRNA expression profiles of 31 primary gastric tumors from the UK patient cohort. Gastric cancer (GC) is the second leading cause of global cancer mortality, with individual gastric tumors displaying significant heterogeneity in their deregulation of various oncogenic pathways. We aim to identify major oncogenic pathways in GC that robustly impact patient survival and treatment response. We used an in silico strategy based on gene expression signatures and connectivity analytics to map patterns of oncogenic pathway activation in 25 unique GC cell lines, and in 301 primary gastric cancers from three independent patient cohorts. Of 11 oncogenic pathways previously implicated in GC, we identified three predominant pathways (proliferation/stem cell, NF-kB, and Wnt/b-catenin) deregulated in the majority (>70%) of gastric tumors. Using a variety of proliferative, Wnt, and NF-kB-related assays, we experimentally validated the pathway predictions in multiple GC cell lines showing similar pathway activation patterns in vitro. Patients stratified at the level of individual pathways did not exhibit consistent differences in clinical outcome. However, patients grouped by oncogenic pathway combinations demonstrated robust and significant survival differences (e.g., high proliferation/high NF-kB vs. low proliferation/low NF-kB), suggesting that tumor behavior in GC is likely influenced by the combined effects of multiple oncogenic pathways. Our results demonstrate that GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Experiment Overall Design: Profiling of 31 primary gastric tumors on Affymetrix GeneChip Human Genome U133 Array Set HG-U133A. All tumors were collected with approvals from the St James's University Hospital, United Kingdom and the Research Ethics Review Committee.
2009-04-10 | E-GEOD-15456 | biostudies-arrayexpress
Project description:Sepsis remains a lethal ailment with imprecise treatment and ill-understood biology. A clinical transcriptomic analysis of sepsis patients was performed for the first time in India and revealed large-scale change in blood gene expression in patients of severe sepsis and septic shock admitted to ICU. Three biological processes were quantified using scores derived from the corresponding transcriptional modules. Comparison of the module scores revealed that genes associated with immune response were more suppressed compared to the inflammation-associated genes. These findings will have great implication in the treatment and prognosis of severe sepsis/septic shock if it can be translated into a bedside tool.
2022-09-12 | GSE137341 | GEO
Project description:Plasmacytoid dendritic cells (pDCs) play a key role in the activation of the autoimmune response in LN. Recently we demonstrated that these cells infiltrate the kidney of patients with LN at tubulointerstitial level. The pDCs are the main producers of IFN-alpha, whose effects on the renal tubule are poorly understood. The aim of the study was to investigate the effects of INF-alpha in renal epithelial cells (RPTEC). We investigated the effect of IFN-alpha on the whole-genome gene expression profile in RPTEC cells,. Genomic analysis showed that after stimulation, 108 genes are up-regulated and only 7 are down-regulated, with a fold-change> 2. The Gene Set Enrichment analysis confirmed that IFN-alpha induced the pathway of antigen presentation and the inflammatory signaling in RPTEC. Among the up-regulated genes involved in these pathways, there were HLA-I, the ubiquitins (FBXO6 and DTX3L) and the immunoproteasome subunits LMP7. We performed the validation of these genes by real time PCR and citometry experiments on RPTEC stimulated with IFN-alpha. Immunohistochemical analysis of LMP7 and MXA protein, specific marker of IFN-alpha, showed a significant upregulatation of both proteins in renal biopsies of patients with LN class IV compared to class I. Confocal microscopy showed the colocalization of LMP7-MXA in tubular epithelium of patients with LN class IV and activation of inflammatory signaling via NF-kB in the MXA+ tubules. Our data suggested that inhibition of INF-alpha pathways could represent a novel therapeutic strategy to reduce renal tubular damage in patients with LN. To identify genes specifically modulated by INF-alpha in RPTEC, we stimulated 3 different cell clones with 100U/ml INF-alpha for 48 hours and compared their whole-genome gene expression profiles with that from 3 RPTEC clones cultured without stimuli.
2015-12-15 | E-GEOD-48551 | biostudies-arrayexpress