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Identification of genes and pathways associated with multiple organ dysfunction syndrome by microarray analysis.

ABSTRACT: Multiple organ dysfunction syndrome (MODS) is characterized by the development of progressive physiological dysfunction of ?2 organs or organ systems and is responsible for the majority of the morbidity and mortality among patients in intensive care units. The aim of the present study was to investigate the potential genes and pathways associated with MODS. The microarray dataset GSE60088 was downloaded from the Gene Expression Omnibus and used to identify differentially expressed genes (DEGs) between organ tissues (lung, liver and kidney) obtained from a murine model of MODS and healthy controls. The interactions between DEGs in lungs, liver and kidneys were revealed by Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Furthermore, protein?protein interaction (PPI) data for DEGs were obtained from the Search Tool for the Retrieval of Interacting Genes and a PPI network was constructed. Additionally, DEGs that were common among the three organs were screened and transcription factors that regulated them were predicted using the iRegulon plugin. A total of 943, 267 and 227 DEGs were identified in lung, liver and kidney samples, respectively, between mice with MODS and healthy controls. In lung and liver samples, two pathways that were enriched with DEGs were identified and were common between lung and liver samples, including 'cytokine?cytokine receptor interaction' and 'Jnk?STAT signaling pathway', and examples of DEGs associated with these pathways include C?X?C motif chemokine ligand (Cxcl)1 and Cxcl10, and signal transducer and activator of transcription (Stat)1, respectively. Furthermore, two common pathways were identified in liver and kidney samples, which included 'MAPK signaling pathway' and 'p53 signaling pathway', and DEGs associated with these pathways included growth arrest and DNA damage?inducible ?. A total of 18 DEGs were common among lung, liver and kidney tissues, including CCAAT/enhancer binding protein ? (Cebpb) and olfactomedin?like 1 (Olfml1). Cebpb modulated various other DEGs, such as Cxcl1, and Olfml1 was regulated by Stat5A. These genes and pathways may serve roles in the progression of MODS and may be considered to be potential therapy targets for MODS.

SUBMITTER: Gu C

PROVIDER: S-EPMC6059685 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Identification of genes and pathways associated with multiple organ dysfunction syndrome by microarray analysis.

Gu Changwei C Qiao Wanhai W Wang Lina L Li Minmin M Song Kang K

Molecular medicine reports 20180504 1

Multiple organ dysfunction syndrome (MODS) is characterized by the development of progressive physiological dysfunction of ≥2 organs or organ systems and is responsible for the majority of the morbidity and mortality among patients in intensive care units. The aim of the present study was to investigate the potential genes and pathways associated with MODS. The microarray dataset GSE60088 was downloaded from the Gene Expression Omnibus and used to identify differentially expressed genes (DEGs) b ...[more]

PMID: 29749505

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Project description:OBJECTIVES:Patterns and outcomes of multiple organ dysfunction syndrome are unknown in critically ill children with hyperglycemia. We aimed to determine whether tight glycemic control to a lower vs. higher range influenced timing, duration, or resolution of multiple organ dysfunction syndrome as well as characterize the clinical outcomes of subgroups of multiple organ dysfunction syndrome in children enrolled in the Heart And Lung Failure-Pediatric INsulin Titration trial. DESIGN:Planned secondary analysis of the multicenter Heart And Lung Failure-Pediatric INsulin Titration trial. SETTING:Thirty-five PICUs. PATIENTS:Critically ill children with hyperglycemia who received the Heart And Lung Failure-Pediatric INsulin Titration protocol from 2012 to 2016. INTERVENTIONS:Randomization to a lower versus higher glucose target group. MEASUREMENTS AND MAIN RESULTS:Of 698 patients analyzed, 48 (7%) never developed multiple organ dysfunction syndrome, 549 (79%) had multiple organ dysfunction syndrome without progression, 32 (5%) developed new multiple organ dysfunction syndrome, and 69 (10%) developed progressive multiple organ dysfunction syndrome. Of those whose multiple organ dysfunction syndrome resolved, 192 (34%) experienced recurrent multiple organ dysfunction syndrome. There were no significant differences in the proportion of multiple organ dysfunction syndrome subgroups between Heart And Lung Failure-Pediatric INsulin Titration glucose target groups. However, patients with new or progressive multiple organ dys function syndrome had fewer ICU-free days through day 28 than those without new or progressive multiple organ dysfunction syndrome, and progressive multiple organ dysfunction syndrome patients had fewer ICU-free days than those with new multiple organ dysfunction syndrome: median 25.1 days for never multiple organ dysfunction syndrome, 20.2 days for multiple organ dysfunction syndrome without progression, 18.6 days for new multiple organ dysfunction syndrome, and 0 days for progressive multiple organ dysfunction syndrome (all comparisons p < 0.001). Patients with recurrent multiple organ dysfunction syndrome experienced fewer ICU-free days than those without recurrence (median, 11.2 vs 22.8 d; p < 0.001). CONCLUSIONS:Tight glycemic control target range was not associated with differences in the proportion of new, progressive, or recurrent multiple organ dysfunction syndrome. New or progressive multiple organ dysfunction syndrome was associated with poor clinical outcomes, and progressive multiple organ dysfunction syndrome was associated with worse outcomes than new multiple organ dysfunction syndrome. In future studies, new multiple organ dysfunction syndrome and progressive multiple organ dysfunction syndrome may need to be considered separately, as they represent distinct subgroups with different, potentially modifiable risk factors. Patients with recurrent multiple organ dysfunction syndrome represent a newly characterized, high-risk group which warrants attention in future research.

Project description:OBJECTIVES:We sought to describe current outcomes of Multiple Organ Dysfunction Syndrome present on day 1 of PICU admission. DESIGN:Retrospective observational cohort study. SETTING:Virtual Pediatric Systems, LLC, database admissions, January 2014 and December 2015. PATIENTS:We analyzed 194,017 consecutive PICU admissions, (age 1 mo to 18 yr) from the 2014-2015 Virtual Pediatric Systems database. INTERVENTIONS:We identified day 1 Multiple Organ Dysfunction Syndrome by International Pediatric Sepsis Consensus Conference criteria with day 1 laboratory and vital sign values. Functional status was evaluated by Pediatric Overall Performance Category and Pediatric Cerebral Performance Category scores from PICU admission and discharge. MEASUREMENTS AND MAIN RESULTS:Overall, PICU mortality was 2.1%. We identified day 1 Multiple Organ Dysfunction Syndrome in 14.4% of admissions. Patients with Multiple Organ Dysfunction Syndrome had higher mortality than those without Multiple Organ Dysfunction Syndrome (10.3% vs 0.7%; p < 0.0001), and a higher percentage of survivors had greater than or equal to 2 category worsening in Pediatric Cerebral Performance Category score (3.6% vs 0.5%; p < 0.0001) or Pediatric Overall Performance Category score (6.0% vs 1.8%; p < 0.0001). The odds of death with day 1 Multiple Organ Dysfunction Syndrome was 14.3 (95% CI, 13-15.7), while the odds of death or discharge with Pediatric Overall Performance Category/Pediatric Cerebral Performance Category score greater than or equal to 3 (poor functional outcome) was 6.7 (95% CI, 6-7.4). In a subset of 148,188 patients from hospitals where limitation of support decisions were recorded, 5.8% patients with Multiple Organ Dysfunction Syndrome had limitation of support decisions in place, compared with 0.8% of patients without Multiple Organ Dysfunction Syndrome (p < 0.0001). Of day 1 Multiple Organ Dysfunction Syndrome patients who died, 43.1% had limitation of support decisions in place, and 41.6% had withdrawal of life-sustaining therapies (p < 0.0001). CONCLUSIONS:Multiple Organ Dysfunction Syndrome present on day 1 of admission continues to be a major source of morbidity and mortality in the PICU, but risk of poor neurologic outcome may be improved. Further research is needed to understand decisions regarding limitation of support and withdrawal of life-sustaining therapy decisions in patients admitted with day 1 Multiple Organ Dysfunction Syndrome.

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Identification of genes and pathways associated with multiple organ dysfunction syndrome by microarray analysis.

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Identification of genes and pathways associated with multiple organ dysfunction syndrome by microarray analysis.

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