Expression of Neutrophil-related genes in patients with early sepsis-induced ARDS
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Alisha Holloway
PROVIDER: E-GEOD-66890 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Clinical study of critically ill patients with sepsis and sepsis-related ARDS with whole blood RNA collected within the first 24 hours of admission Goal of the study was to determine whether biologically relevant genes were identified to be differentially expressed genes in patients with sepsis alone and sepsis with ARDS
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Project description:Background: COVID-19 and sepsis represent formidable public health challenges, characterized by incompletely elucidated molecular mechanisms. Elucidating the interplay between COVID-19 and sepsis, particularly in geriatric patients suffering from sepsis-induced acute respiratory distress syndrome (ARDS), is of paramount importance for identifying potential therapeutic interventions to mitigate hospitalization and mortality risks.We employed bioinformatics and systems biology approaches to identify hub genes, shared pathways, molecular biomarkers, and candidate therapeutics for managing COVID-19, sepsis, and sepsis-induced ARDS. We corroborated these hub genes utilizing murine sepsis-ARDS models and blood samples derived from geriatric patients afflicted by sepsis-induced ARDS.Results: Our investigation revealed 189 differentially expressed genes (DEGs) shared among COVID-19 and sepsis datasets. We constructed a protein-protein interaction network, unearthing pivotal hub genes and modules. Notably, nine hub genes displayed significant alterations and correlations with critical inflammatory mediators of pulmonary injury in murine septic lungs. Simultaneously, 12 displayed significant changes and correlations with a neutrophil-recruiting chemokine in geriatric patients with sepsis-induced ARDS. Of these, six hub genes (CD247, CD2, CD40LG, KLRB1, LCN2, RETN) showed significant alterations across COVID-19, sepsis, and geriatric sepsis-induced ARDS. Our single-cell RNA sequencing analysis of hub genes across 3 diverse immune cell types furnished insights into disease pathogenesis. Functional analysis underscored the interconnection between sepsis/sepsis-ARDS and COVID-19, enabling us to pinpoint potential therapeutic targets, transcription factor-gene interactions, DEG-microRNA co-regulatory networks, and prospective drug and chemical compound interactions involving hub genes.Our investigation offers potential therapeutic targets/biomarkers, sheds light on the immune response in geriatric patients with sepsis-induced ARDS, emphasizes the association between sepsis/sepsis-ARDS and COVID-19, and proposes novel avenues for targeted therapies.
2023-09-01 | GSE242127 | GEO
Project description:Both sepsis and acute respiratory distress syndrome (ARDS) rely on imprecise clinical definitions leading to heterogeneity, which has contributed to negative trials. Because circulating protein/DNA complexes have been implicated in sepsis and ARDS, we aimed to develop a proteomic signature of DNA-bound proteins to discriminate between children with sepsis with and without ARDS. We performed a prospective case-control study in 12 children with sepsis with ARDS matched to 12 children with sepsis without ARDS on age, severity of illness score, and source of infection. We performed co-immunoprecipitation and downstream proteomics in plasma collected ≤ 24 h of intensive care unit admission. Expression profiles were generated, and a random forest classifier was used on differentially expressed proteins to develop a signature which discriminated ARDS. The classifier was tested in six independent blinded samples. Neutrophil and nucleosome proteins were over-represented in ARDS, including two S100A proteins, superoxide dismutase (SOD), and three histones. Random forest produced a 10-protein signature that accurately discriminated between children with sepsis with and without ARDS. This classifier perfectly assigned six independent blinded samples as having ARDS or not. We validated higher expression of the most informative discriminating protein, galectin-3-binding protein, in children with ARDS. Our methodology has applicability to isolation of DNA-bound proteins from plasma. Our results support the premise of a molecular definition of ARDS, and give preliminary insight into why some children with sepsis, but not others, develop ARDS.
2024-02-14 | PXD049377 | Pride
Project description:A microarray analysis involving whole blood samples isolated from critically ill patients in the medical intensive care unit at Brigham and Women's Hospital. Four groups of intubated subjects undergoing mechanical ventilation were recruited for the study: those with sepsis alone (Sepsis), those with sepsis + ARDS (se/ARDS), those with SIRS (SIRS), and those whithout sepsis, SIRS, or ARDS (untreated). Blood was obtained from patients on the day of admission (day 0) and 7 days later. RNA was isolated from the whole blood samples and microarrays were prepared to determine differential gene expression between the four groups. Total RNA obtained from whole blood samples of critically ill patients
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Project description:To investigate the transcriptomic changes associated with ARDS progression, we performed RNA-seq on PBMCs from 6 healthy donors (Con), 7 ARDS patients
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Project description:The acute respiratory distress syndrome (ARDS) is a highly lethal syndrome characterized by hypoxemia and bilateral lung infiltrates in response to an inciting event such as sepsis. Allogeneic bone marrow transplantation (BMT) is a life-saving treatment for patients with hematologic malignancies that can be complicated by ARDS. We sought to identify blood gene expression signatures that distinguish whether ARDS in BMT may be a distinct pathobiologic entity from ARDS in non-BMT patients. RNA-Seq was used to measure whole blood transcript expression differences between 26 patients meeting the Berlin definition of ARDS: 8 patients without BMT and 5 BMT patients with ARDS from the Brigham and Women’s Registry of Critical Illness (RoCI), as well as 7 non-BMT patients with sepsis and 6 BMT patients with sepsis. RNA was globin cleared using the Ambion GLOBINclear kit prior to preparation of poly(A)-selected RNA-Seq libraries with the Illumina TruSeq method. An Illumina HiSeq 2500 instrument was used to generate 75 base pair paired-end reads, which were aligned to the hg38 reference genome using STAR. Differential expression analysis was performed using DESeq2.
2018-12-31 | GSE84439 | GEO
Project description:SARS-CoV-2 is a novel coronavirus that causes acute respiratory distress syndrome (ARDS), death and long-term sequelae. Innate immune cells are critical for host defense but are also the primary drivers of ARDS. The relationships between innate cellular responses in ARDS resulting from COVID-19 compared to other causes of ARDS, such as bacterial sepsis is unclear. Moreover, the beneficial effects of dexamethasone therapy during severe COVID-19 remain speculative, but understanding the mechanistic effects could improve evidence-based therapeutic interventions. To interrogate these relationships, we developed an scRNAseq atlas that is freely accessible (biernaskielab.ca/COVID_neutrophil). We discovered that compared to bacterial ARDS, COVID-19 was associated with distinct neutrophil polarization characterized by either interferon (IFN) or prostaglandin (PG) active states. Neutrophils from bacterial ARDS had higher expression of antibacterial molecules such as PLAC8 and CD83. Dexamethasone therapy in COVID patients rapidly altered the IFNactive state, downregulated interferon responsive genes, and activated IL1R2+ve neutrophils. Dexamethasone also induced the emergence of immature neutrophils expressing immunosuppressive molecules ARG1 and ANXA1, which were not present in healthy controls. Moreover, dexamethasone remodeled global cellular interactions by changing neutrophils from information receivers into information providers. Importantly, male patients had higher proportions of IFNactive neutrophils and a greater degree of steroid-induced immature neutrophil expansion. Indeed, the highest proportion of IFNactive neutrophils was associated with mortality. These results define neutrophil states unique to COVID-19 when contextualized to other life-threatening infections, thereby enhancing the relevance of our findings at the bedside. Furthermore, the molecular benefits of dexamethasone therapy are also defined. The identified molecular pathways can now be targeted to develop improved therapeutics.
2021-10-05 | PXD028429 | Pride
Project description:The ARDS, Pneumonia, and Sepsis (APS) Consortium
| PRJNA1415814 | ENA
Project description:The ARDS, Pneumonia, and Sepsis (APS) Consortium
| PRJNA1415813 | ENA
Project description:Background: Inter-patient prostate cancer (PrCa) heterogeneity results in highly variable patient outcomes. Multi-purpose biomarkers to dissect this heterogeneity are urgently required to improve treatment and accelerate drug development in PrCa. Circulating biomarkers are most practical for evaluating this disease. We pursued the analytical validation and clinical qualification of blood mRNA expression arrays. Methods: Whole blood samples were collected into PaxGeneTM tubes from PrCa patients: 31 good prognosis patients selected for active surveillance (AS) and 63 advanced castration resistant PrCa (CRPC) patients. RNA was extracted, amplified, biotinylated, and hybridised to Affymetrix U133plus2 microarrays and analysis of genome-wide expression profiles were analysed using Bayesian Latent Process Decomposition (LPD). Findings: LPD analysis of the mRNA expression data divided the evaluable patients (n=94) into 4 separate groups. LPD1 and LPD2 consisted almost entirely of CRPC patients (14/14; 17/18); LPD3 (15/31) and LDP4 (12/21) comprised both AS and CRPC. Ten patients were unclassifiable by LPD analysis. LPD1 CRPC patients had significantly poorer overall survival (median 10.7 months, CI-95% 4.2-17.2) than CRPC patients in LPD2 to 4 (median 26.5 months, CI-95% 18.1-34.9, p=0.00007). LPD 1 membership remained the strongest prognostic factor in a multivariate analysis (HR 5.0, CI-95% 2.1-11.9, p=0.0002). Gene signatures in the poor prognosis LPD group 1 were associated with increased CD71+ early erythroid cells and decreased B-cell and T-cell immune response. A 9-gene signature, that was validated by RT-PCR studies, classified patients as group LPD 1 with a very low misclassification rate (1.2%). Interpretation: Poor PrCa outcome can be predicted using gene expression signatures from whole blood and merits further evaluation in predictive and pharmacodynamic biomarker studies for novel anticancer drugs including immune therapies. 107 blood samples were collected in paxgene tubes from 94 prostate cancer patients (31 good prognosis & 63 advanced castration resistant PrCa). Replicates include 9 biological replicates and four technical replicates
2012-10-15 | E-GEOD-37199 | biostudies-arrayexpress