T cell and Monocyte Specific RNAseq Analysis in Septic and Non Septic Critically-Ill Patients and in Patients with Cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE133822 | GEO | 2019/07/29
REPOSITORIES: GEO
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Project description:Sepsis is a frequent complication in critically ill patients and highly heterogeneous that is associated with high morbidity and mortality rates, especially in the elderly population. Utilizing RNA-Sequencing (RNA-Seq) to analysis biological pathways is widely used in clinical and molecular genetics studies, but in elderly patients with sepsis are still lacking. Hence, we aim to investigate the mortality-relevant biological features and transcriptomic features in elderly patients who were admitted to intensive care unit (ICU) for sepsis.
2022-11-03 | GSE216902 | GEO
Project description:Objective: It is unclear whether the host response of gram-positive sepsis differs from gram-negative sepsis at a transcriptome level. Using microarray technology, we compared the gene-expression profiles of gram-positive sepsis and gram-negative sepsis in critically ill patients. Design: A prospective cross-sectional study. Setting: A 20-bed general intensive care unit of a tertiary referral hospital. Patients: Seventy-two patients admitted to the intensive care unit. Interventions: Intravenous blood was collected for leukocyte separation and RNA extraction. Microarray experiements were then performed examing the expression level of 19,232 genes in each sample. Measurements and Main Results: There was no difference in the expression profile between gram-positive and gram-negative sepsis. The finding remained unchanged even when genes with lower expression level were included or after statistical stringency was lowered. There were, however, ninety-four genes differentially expressed between sepsis and control patients. These genes included those involved in immune regulation, inflammation and mitochondrial function. Hierarchical cluster analysis confirmed that the difference in gene expression profile existed between sepsis and control patients, but not between gram-positive and gram-negative patients. Conclusion: Gram-positive and gram-negative sepsis share a common host response at a transcriptome level. These findings support the hypothesis that the septic response is non-specific and is designed to provide a more general response that can be elicited by a wide range of different micro-organisms. The study included seventy-two critically ill patients admitted to the intensive care unit (ICU) of Nepean Hospital, Sydney, Australia. Of these, fifty-five patients were diagnosed to have sepsis, as confirmed by microbiological culture. The remaining seventeen patients did not have sepsis and were therefore used as controls. The study was approved by the hospital ethics committee and informed consent was obtained from all patients or their relatives. Patient Samples. Whole blood was taken from each patient on admission to ICU. Neutrophils were separated from whole blood using density-gradient separation with Ficoll-PaqueP P(Amersham). Subsequent neutrophil RNA extraction was performed using guanidinium thiocyanate (Ambion). Microarray Experiment. The neutrophil RNA was converted to cDNA, fluorescently labeled and hybridized to its complimentary sequences on the microarray (Invitrogen). The fluorescent signals on each micrroarray were captured using the GenePix 4000B laser scanner (Axon Instruments). Expression level of each gene was represented by the intensity of its fluorescent signal. Data Extraction. All signal intensity values were processed using background-subtraction method. Prior to analysis, all values were log-transformed and normalized by fitting a print-tip group Lowess curve. Normalization minimizes bias due to dye chemistry, signal intensity or location of a gene on the array. It ensures the detection of genes that are truly differentially expressed, instead of those caused by experimental artifacts or variation in the hybridization process. After normalization, genes that had more than 50% of data missing were removed. We then selected genes that had at least 80% of the data showing two-fold changes from the geneâs median values. After filtering, 1617 genes were available for further analysis.
2010-05-25 | E-GEOD-6535 | biostudies-arrayexpress
Project description:Objective: It is unclear whether the host response of gram-positive sepsis differs from gram-negative sepsis at a transcriptome level. Using microarray technology, we compared the gene-expression profiles of gram-positive sepsis and gram-negative sepsis in critically ill patients. Design: A prospective cross-sectional study. Setting: A 20-bed general intensive care unit of a tertiary referral hospital. Patients: Seventy-two patients admitted to the intensive care unit. Interventions: Intravenous blood was collected for leukocyte separation and RNA extraction. Microarray experiements were then performed examing the expression level of 19,232 genes in each sample. Measurements and Main Results: There was no difference in the expression profile between gram-positive and gram-negative sepsis. The finding remained unchanged even when genes with lower expression level were included or after statistical stringency was lowered. There were, however, ninety-four genes differentially expressed between sepsis and control patients. These genes included those involved in immune regulation, inflammation and mitochondrial function. Hierarchical cluster analysis confirmed that the difference in gene expression profile existed between sepsis and control patients, but not between gram-positive and gram-negative patients. Conclusion: Gram-positive and gram-negative sepsis share a common host response at a transcriptome level. These findings support the hypothesis that the septic response is non-specific and is designed to provide a more general response that can be elicited by a wide range of different micro-organisms. Keywords: disease state analysis, gram-positive sepsis, gram-negative sepsis
2007-12-01 | GSE6535 | GEO
Project description:The host response in critically ill patients with sepsis, septic shock remains poorly defined. Considerable research has been conducted to accurately distinguish patients with sepsis from those with non-infectious causes of disease. Technological innovations have positioned systems biology at the forefront of biomarker discovery. Analysis of the whole-blood leukocyte transcriptome enables the assessment of thousands of molecular signals beyond simply measuring several proteins in plasma, which for use as biomarkers is important since combinations of biomarkers likely provide more diagnostic accuracy than the measurement of single ones or a few. Evidence suggests that genome-wide transcriptional profiling of blood leukocytes can assist in differentiating between infection and non-infectious causes of severe disease. Of importance, RNA biomarkers have the potential advantage that they can be measured reliably in rapid quantitative reverse transcriptase polymerase chain reaction (qRT-PCR)-based point of care tests. PAXgene blood RNA was isolated at intensive-care unit (ICU) admission and throughout ICU length-of-stay. Through the use of genome-wide microarrays we aimed to identify molecular features that enbale the adequate discrimination of infectious and non-infectious sources of critical illness. Moreover, biological pathway analysis was used to tease out the most relevant biological units in sepsis and septic shock.
2015-07-06 | E-GEOD-65682 | biostudies-arrayexpress
Project description:T cell and Monocyte Specific RNAseq Analysis in Septic and Non Septic Critically-Ill Patients and in Patients with Cancer
| PRJNA552599 | ENA
Project description:The PREVAIL study was a Phase II/III randomized controlled trial examining the use of lactoferrin to prevent nosocomial infections in critically ill patients undergoing mechanical ventilation. Gene expression data was generated from a consecutive subset of patients at the lead study site. We used the Affymetrix PrimeView array to generate expression data at various time points during the ICU stay.
2018-08-22 | GSE118657 | GEO
Project description:The host response in critically ill patients with sepsis, septic shock remains poorly defined. Considerable research has been conducted to accurately distinguish patients with sepsis from those with non-infectious causes of disease. Technological innovations have positioned systems biology at the forefront of biomarker discovery. Analysis of the whole-blood leukocyte transcriptome enables the assessment of thousands of molecular signals beyond simply measuring several proteins in plasma, which for use as biomarkers is important since combinations of biomarkers likely provide more diagnostic accuracy than the measurement of single ones or a few. Evidence suggests that genome-wide transcriptional profiling of blood leukocytes can assist in differentiating between infection and non-infectious causes of severe disease. Of importance, RNA biomarkers have the potential advantage that they can be measured reliably in rapid quantitative reverse transcriptase polymerase chain reaction (qRT-PCR)-based point of care tests.
2015-07-06 | GSE65682 | GEO
Project description:Background: Systemic inflammation is a whole body reaction that can have an infection-positive (i.e. sepsis) or infection-negative origin. It is important to distinguish between septic and non-septic presentations early and reliably, because this has significant therapeutic implications for critically ill patients. We hypothesized that a molecular classifier based on a small number of RNAs expressed in peripheral blood could be discovered that would: 1) determine which patients with systemic inflammation had sepsis; 2) be robust across independent patient cohorts; 3) be insensitive to disease severity; and 4) provide diagnostic utility. The overall goal of this study was to identify and validate such a molecular classifier. Methods and Findings: We conducted an observational, non-interventional study of adult patients recruited from tertiary intensive care units (ICU). Biomarker discovery was conducted with an Australian cohort (n = 105) consisting of sepsis patients and post -surgical patients with infection-negative systemic inflammation. Using this cohort, a four-gene classifier consisting of a combination of CEACAM4, LAMP1, PLA2G7 and PLAC8 RNA biomarkers was identified. This classifier, designated SeptiCyte® Lab, was externally validated using RT-qPCR and receiver operating characteristic (ROC) curve analysis in five cohorts (n = 345) from the Netherlands. Cohort 1 (n=59) consisted of unambiguous septic cases and infection-negative systemic inflammation controls; SeptiCyte® Lab gave an area under curve (AUC) of 0.96 (95% CI: 0.91-1.00). ROC analysis of a more heterogeneous group of patients (Cohorts 2-5; 249 patients after excluding 37 patients with infection likelihood possible) gave an AUC of 0.89 (95% CI: 0.85-0.93). Disease severity, as measured by Sequential Organ Failure Assessment (SOFA) score or the Acute Physiology and Chronic Health Evaluation (APACHE) IV score, was not a significant confounding variable. The diagnostic utility o f SeptiCyte® Lab was evaluated by comparison to various clinical and laboratory parameters that would be available to a clinician within 24 hours of ICU admission. SeptiCyte® Lab was significantly better at differentiating sepsis from infection-negative systemic inflammation than all tested parameters, both singly and in various logistic combinations. SeptiCyte® Lab more than halved the diagnostic error rate compared to PCT in all tested cohorts or cohort combinations. Conclusions: SeptiCyte® Lab is a rapid molecular assay that may be clinically useful in the management of ICU patients with systemic inflammation. SIRS and Sepsis ICU patients, admission samples Retrospective, mutli-site sutdy using retrospective physician adjudication as a comparator
2015-10-24 | E-GEOD-74224 | biostudies-arrayexpress
Project description:Sepsis is characterized as life-threatening organ dysfunction caused by a dysregulated host immune response to infection. The purpose of this investigation was to determine the differential effect of sepsis on innate versus adaptive immunity, in humans, by examining RNA expression in specific immune cell subsets, including monocytes/macrophages and CD4 and CD8 T cells. A second aim was to determine immunosuppressive mechanisms operative in sepsis that might be amenable to immunotherapy. Finally, we examined RNA expression in peripheral cells from critically ill nonseptic patients and from cancer patients to compare the unique immune response in these disorders with that occurring in sepsis. Monocytes, CD4 T cells, and CD8 T cells from septic patients, critically ill nonseptic patients, patients with metastatic colon cancer, and healthy controls were analyzed by RNA sequencing. Sepsis induced a marked phenotypic shift toward downregulation of multiple immune response pathways in monocytes suggesting that impaired innate immunity may be fundamental to the immunosuppression that characterizes the disorder. In the sepsis cohort, there was a much more pronounced effect on gene transcription in CD4 T cells than in CD8 T cells. Potential mediators of sepsis-induced immunosuppression included Arg-1, SOCS-1, and SOCS-3, which were highly upregulated in multiple cell types. Multiple negative costimulatory molecules, including TIGIT, Lag-3, PD-1, and CTLA-4, were also highly upregulated in sepsis. Although cancer had much more profound effects on gene transcription in CD8 T cells, common immunosuppressive mechanisms were present in all disorders, suggesting that immunoadjuvant therapies that are effective in one disease may also be efficacious in the others.
| S-EPMC6761013 | biostudies-literature
Project description:BACKGROUND:Associations among inflammatory cytokines, erythropoietin (EPO), and anemia in critically ill septic patients remain unclear. This study tested the hypothesis that elevated inflammatory cytokines and decreased EPO would be associated with iron-restricted anemia while accounting for operative blood loss, phlebotomy blood loss, and red blood cell (RBC) transfusion volume. METHODS:Prospective observational cohort study of 42 critically ill septic patients was conducted. Hemoglobin (Hb) at sepsis onset and hospital discharge were used to calculate ?Hb. Operative blood loss, phlebotomy blood loss, and RBC transfusion volume were used to calculate adjusted ?Hb (Adj?Hb) assuming that 300 mL RBC is equal to 1 g/dL Hb. Patients with Adj?Hb of greater than 0 (positive Adj?Hb, n = 18) were compared with patients with Adj?Hb of less than or equal to 0 (negative Adj?Hb, n = 24). RESULTS:Plasma tumor necrosis factor ?, granulocyte colony-stimulating factor, interleukin (IL)-6, IL-8, EPO, erythrocyte mean corpuscular volume, and serum transferrin receptor were measured on days 0, 1, 4, 7, and 14. Patients with negative Adj?Hb had significantly higher day 14 levels of IL-6 (37.4 vs. 15.2 pg/mL, p < 0.05), IL-8 (39.1 vs. 18.2 pg/mL, p = 0.01), and granulocyte colony-stimulating factor (101.3 vs. 60.5 pg/mL, p = 0.01), but not EPO. On linear regression analysis, lower Adj?Hb was associated with higher day 14 levels of IL-6 (r = 0.22, p < 0.01), IL-8 (r = 0.10, p = 0.04), stromal cell-derived factor 1 (r = 0.14, p = 0.02), and tumor necrosis factor ? (r = 0.13, p = 0.02), but not EPO. Patients with negative Adj?Hb had significantly lower mean corpuscular volume on days 4 (89.6 vs. 93.2 fL/cell, p = 0.04), 7 (92.3 vs. 94.9 fL/cell, p = 0.04), and 14 (92.1 vs. 96.0 fL/cell, p = 0.03) but similar serum transferrin receptor levels. CONCLUSION:Persistent elevation of inflammatory cytokines was associated with iron-restricted anemia among critically ill septic patients, occurring in the absence of systemic iron deficiency, independent of endogenous EPO. LEVEL OF EVIDENCE:Prognostic study, level II.
| S-EPMC6410351 | biostudies-literature