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Gene expression in peripheral mononuclear cells from septic patients secondary to community acquired pneumonia: patterns of gene expression and outcomes - GSE48080

Purpose

Sepsis is defined as a systemic inflammatory response secondary to a proven or suspected infection. Mechanisms governing this inflammatory response have been shown to be complex and dynamic, involving cross-talking among diverse signaling pathways. However, current knowledge on mechanisms underlying sepsis is far from providing a complete picture of the syndrome, justifying additional efforts that might add to this scenario. Microarray-based expression profiling is a powerful approach for the investigation of complex clinical conditions such as sepsis: the analysis of gene transcription at the genome level potentially avoids results derived from biased assumptions. In this study we investigate whole-genome gene expression profiles of mononuclear cells from survivor and non-survivor septic patients. Blood samples were collected at the time of sepsis diagnosis and seven days later, allowing us to evaluate the role of biological processes or genes possibly involved in patient recovery. Aiming to circumvent, at least partially, the heterogeneity of septic patients we included only patients admitted with sepsis caused by community-acquired pneumonia. Global gene expression profiling allowed us to characterize early sepsis, as compared to healthy individuals. Our results corroborate literature reports on inflammation response in the early stages of sepsis but highlight great heterogeneity in gene expression during sepsis progress. Additionally, global gene expression in the early stage was also able to distinguish sepsis from septic shock and correlated with patient outcome. Differences in oxidative stress seem to be associated with clinical outcome, since significant differences in the expression profile of related genes were observed between survivors and non-survivors at the time of patient enrollment (early sepsis). However, our results substantiate current knowledge supporting that sepsis syndrome development is indeed multifaceted. Although the initial infection of enrolled patients was pneumonia, seven days later gene expression profiles seemed to be characteristic of each patient, common gene expression changes distinguishing survivors from non-survivors. This result could be associated with the underlying health status of each one of them, with complications due to sepsis itself as well as with distinct timing for response to treatment.

Hypothesis

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Experimental Design

In this study we investigate whole-genome gene expression profiles of mononuclear cells from survivor (n=5) and non-survivor (n=5) septic patients, as well as from 3 healthy controls. Blood samples were collected at the time of sepsis diagnosis and seven days later, allowing us to evaluate the role of biological processes or genes possibly involved in patient recovery. Aiming to circumvent, at least partially, the heterogeneity of septic patients we included only patients admitted with sepsis caused by community-acquired pneumonia.

Experimental Variables

Sepsis (2021 ICD-10-CM code* = A41)

Septic shock (2021 ICD-10-CM code* = R65.21)

Controls

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Methods

The scanned images were analyzed with Feature Extraction Software v 9.5.1 (Agilent) using default parameters to obtain background subtracted and spatially detrended Processed Signal intensities. Features flagged in Feature Extraction as Feature Non-uniform outliers were excluded.

Additional Information

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE48080

Microarray
Agilent 014850 v1
23 Samples Loaded: 23
Human (Homo sapiens)
PBMC
Sepsis, Septic shock
Sample Set Spreadsheet
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Samples Preview
Sample ID !Sample Title diagnosis Cell type outcome Time point
GSM1167513 P107_D0 Septic shock mononuclear cells Alive D0 (at the time of sepsis diagnosis)
GSM1167514 P107_D7 Septic shock mononuclear cells Alive D7 (7 days after diagnosis)
GSM1167515 P140_D0 Severe sepsis mononuclear cells Alive D0 (at the time of sepsis diagnosis)
GSM1167516 P140_D7 Severe sepsis mononuclear cells Alive D7 (7 days after diagnosis)
GSM1167517 P143_D0 Severe sepsis mononuclear cells Alive D0 (at the time of sepsis diagnosis)
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sampleset4000191_sampleannotations.csv
Sample Set Spreadsheet
sampleset4000191_sampleannotations.csv
Sample Set Spreadsheet
Raw Signal
Raw Signal
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Sample ID !Sample Title Diagnosis Cell type Outcome Time point Grouping D0 Vs HC Grouping S Vs NS D0 Grouping Survivors D0vsD7 Grouping NonSurvivors D0vsD7 Grouping Survivors D7 NonSurvivors D7 Grouping Disease
GSM1167513
P107_D0
Septic shock
mononuclear cells
Alive
D0 (at the time of sepsis diagnosis)
D0
D0_Survivor
D0_Survivor
D0_Survivor
D0_Survivor
Sepsis related
GSM1167514
P107_D7
Septic shock
mononuclear cells
Alive
D7 (7 days after diagnosis)
D7
D7_Survivor
D7_Survivor
D7_Survivor
D7_Survivor
Sepsis related
GSM1167515
P140_D0
Severe sepsis
mononuclear cells
Alive
D0 (at the time of sepsis diagnosis)
D0
D0_Survivor
D0_Survivor
D0_Survivor
D0_Survivor
Sepsis related
GSM1167516
P140_D7
Severe sepsis
mononuclear cells
Alive
D7 (7 days after diagnosis)
D7
D7_Survivor
D7_Survivor
D7_Survivor
D7_Survivor
Sepsis related
GSM1167517
P143_D0
Severe sepsis
mononuclear cells
Alive
D0 (at the time of sepsis diagnosis)
D0
D0_Survivor
D0_Survivor
D0_Survivor
D0_Survivor
Sepsis related
GSM1167518
P143_D7
Severe sepsis
mononuclear cells
Alive
D7 (7 days after diagnosis)
D7
D7_Survivor
D7_Survivor
D7_Survivor
D7_Survivor
Sepsis related
GSM1167519
P146_D0
Septic shock
mononuclear cells
Dead
D0 (at the time of sepsis diagnosis)
D0
D0_Non-Survivor
D0_Non-Survivor
D0_Non-Survivor
D0_Non-Survivor
Sepsis related
GSM1167520
P146_D7
Septic shock
mononuclear cells
Dead
D7 (7 days after diagnosis)
D7
D7_Non-Survivor
D7_Non-Survivor
D7_Non-Survivor
D7_Non-Survivor
Sepsis related
GSM1167521
P217_D0
Severe sepsis
mononuclear cells
Dead
D0 (at the time of sepsis diagnosis)
D0
D0_Non-Survivor
D0_Non-Survivor
D0_Non-Survivor
D0_Non-Survivor
Sepsis related
GSM1167522
P217_D7
Severe sepsis
mononuclear cells
Dead
D7 (7 days after diagnosis)
D7
D7_Non-Survivor
D7_Non-Survivor
D7_Non-Survivor
D7_Non-Survivor
Sepsis related
GSM1167523
P227_D0
Septic shock
mononuclear cells
Dead
D0 (at the time of sepsis diagnosis)
D0
D0_Non-Survivor
D0_Non-Survivor
D0_Non-Survivor
D0_Non-Survivor
Sepsis related
GSM1167524
P227_D7
Septic shock
mononuclear cells
Dead
D7 (7 days after diagnosis)
D7
D7_Non-Survivor
D7_Non-Survivor
D7_Non-Survivor
D7_Non-Survivor
Sepsis related
GSM1167525
P229_D0
Severe sepsis
mononuclear cells
Alive
D0 (at the time of sepsis diagnosis)
D0
D0_Survivor
D0_Survivor
D0_Survivor
D0_Survivor
Sepsis related
GSM1167526
P229_D7
Severe sepsis
mononuclear cells
Alive
D7 (7 days after diagnosis)
D7
D7_Survivor
D7_Survivor
D7_Survivor
D7_Survivor
Sepsis related
GSM1167527
P239_D0
Septic shock
mononuclear cells
Dead
D0 (at the time of sepsis diagnosis)
D0
D0_Non-Survivor
D0_Non-Survivor
D0_Non-Survivor
D0_Non-Survivor
Sepsis related
GSM1167528
P239_D7
Septic shock
mononuclear cells
Dead
D7 (7 days after diagnosis)
D7
D7_Non-Survivor
D7_Non-Survivor
D7_Non-Survivor
D7_Non-Survivor
Sepsis related
GSM1167529
P254_D0
Septic shock
mononuclear cells
Dead
D0 (at the time of sepsis diagnosis)
D0
D0_Non-Survivor
D0_Non-Survivor
D0_Non-Survivor
D0_Non-Survivor
Sepsis related
GSM1167530
P254_D7
Septic shock
mononuclear cells
Dead
D7 (7 days after diagnosis)
D7
D7_Non-Survivor
D7_Non-Survivor
D7_Non-Survivor
D7_Non-Survivor
Sepsis related
GSM1167531
P260_D0
Severe sepsis
mononuclear cells
Alive
D0 (at the time of sepsis diagnosis)
D0
D0_Survivor
D0_Survivor
D0_Survivor
D0_Survivor
Sepsis related
GSM1167532
P260_D7
Severe sepsis
mononuclear cells
Alive
D7 (7 days after diagnosis)
D7
D7_Survivor
D7_Survivor
D7_Survivor
D7_Survivor
Sepsis related
GSM1167533
Control 1
Healthy volunteer
mononuclear cells
Healthy volunteer
Healthy volunteer
Healthy
Healthy
Healthy
Healthy
Healthy
Healthy
GSM1167534
Control 2
Healthy volunteer
mononuclear cells
Healthy volunteer
Healthy volunteer
Healthy
Healthy
Healthy
Healthy
Healthy
Healthy
GSM1167535
Control 3
Healthy volunteer
mononuclear cells
Healthy volunteer
Healthy volunteer
Healthy
Healthy
Healthy
Healthy
Healthy
Healthy

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