Gene expression in peripheral mononuclear cells from septic patients secondary to community acquired pneumonia: patterns of gene expression and outcomes - GSE48080
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.
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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.
Sepsis (2021 ICD-10-CM code* = A41)
Septic shock (2021 ICD-10-CM code* = R65.21)
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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.
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE48080
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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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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Severity All days | Default | View |
Timepoints | View | |
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All days vs Healthy control | |
Group | |
Severity All days | |
Timepoints |