Sample Set Annotation Tool: Skeletal muscle transcriptome in ICU patient suffering from sepsis induced multiple organ failure - GSE13205 [Sepsis induced multiple organ failure (MOF)]

Study Design
Assay
Sample Info
Files
Info
Samples
Group Sets
Analysis

Purpose

Septic patients treated in the intensive care unit (ICU) often develop multiple organ failure including persistent skeletal muscle dysfunction which results in the patient’s protracted recovery process. We have demonstrated that muscle mitochondrial enzyme activities are impaired in septic ICU patients resulting in decreased cellular energy which will interfere with muscle function and metabolism. Here we use detailed phenotyping and genomics to elucidate mechanisms leading to these impairments. Methodology/Principle Findings Utilising biopsy material from seventeen patients and ten age-matched controls we demonstrate that neither mitochondrial in vivo protein synthesis nor expression of mitochondrial genes are compromised. Indeed, there was partial activation of the mitochondrial biogenesis pathway involving NRF2?/GABP and its target genes TFAM, TFB1M and TFB2M yet clearly this failed to maintain mitochondrial function. We therefore utilised transcript profiling and pathway analysis of ICU patient skeletal muscle to generate insight into the molecular defects driving loss of muscle function and metabolic homeostasis. Gene ontology analysis of Affymetrix analysis demonstrated substantial loss of muscle specific genes, a global oxidative stress response related to most probably cytokine signalling, altered insulin related signalling and a substantial overlap between patients and muscle wasting/inflammatory animal models. MicroRNA 21 processing appeared defective suggesting that post-transcriptional protein synthesis regulation is altered by disruption of tissue microRNA expression. Finally, we were able to demonstrate that the phenotype of skeletal muscle in ICU patients is not merely one of inactivity, it appears to be an actively remodelling tissue, influenced by several mediators, all of which may be open to manipulation with the aim to improve clinical outcome. Conclusions/Significance This first combined protein and transcriptome based analysis of human skeletal muscle obtained from septic patients demonstrated that losses of mitochondria and muscle mass are accompanied by sustained protein synthesis (anabolic process) while dysregulation of transcription programmes appears to fail to compensate for increased damage and proteolysis. Our analysis identified both validated and novel clinically tractable targets to manipulate these failing processes and pursuit of these could lead to new potential treatments.

Hypothesis

Experimental Design

13 septic samples, 8 controls

Experimental Variables

Sepsis induced multiple organ failure (2021 ICD-10-CM code* = A41)

Controls

Methods

Data presented in the paper was quality controlled using the Microarray Suite software (MAS 5.0). All array data were normalized through implementations of the MAS5 algorithm, to a global scaling intensity of 100. Probesets declared absent by MAS5 across all chips were removed from further analysis.

Additional Information

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13205

Expected Samples:

21 Samples Loaded: 21

Species

Human (Homo sapiens)

Sample Source

vastus lateralis

Disease

Sepsis induced multiple organ failure

Treatment Protocol

Growth Protocol

Extraction Protocol

Total RNA was isolated from muscle samples using TRIzol (Invitrogen, Stockholm, Sweden) and quantified using a Nano-drop spectrophotometer.

Storage Conditions

Sample Set Spreadsheet

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Samples Preview

Sample ID	!Sample Title	Age	Gender	Grouping
GSM333436	Muscle septic k49	60	male, Age:60	Septic Patient
GSM333437	Muscle septic k50	46	male, Age:46	Septic Patient
GSM333438	Muscle septic k53	77	male, Age:77	Septic Patient
GSM333439	Muscle septic k54	56	female, Age:56	Septic Patient
GSM333440	Muscle septic k55	77	male, Age:77	Septic Patient

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File
sampleset4000218_sampleannotations_GSE13205.csv Sample Set Spreadsheet
sampleset4000218_sampleannotations_v1.csv Sample Set Spreadsheet
sampleset4000218_sampleannotations_v1.csv Sample Set Spreadsheet

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Sample ID	!Sample Title	Age	Gender	Grouping
GSM333436	Muscle septic k49	60	male, Age:60	Septic Patient
GSM333437	Muscle septic k50	46	male, Age:46	Septic Patient
GSM333438	Muscle septic k53	77	male, Age:77	Septic Patient
GSM333439	Muscle septic k54	56	female, Age:56	Septic Patient
GSM333440	Muscle septic k55	77	male, Age:77	Septic Patient
GSM333441	Muscle septic k56	69	female, Age:69	Septic Patient
GSM333442	Muscle septic k57	77	male, Age:77	Septic Patient
GSM333443	Muscle septic k59	74	male, Age:74	Septic Patient
GSM333444	Muscle septic k60	67	female, Age:67	Septic Patient
GSM333445	Muscle septic k61	77	male, Age:77	Septic Patient
GSM333446	Muscle septic k62	48	male, Age:48	Septic Patient
GSM333447	Muscle septic k63	71	female, Age:71	Septic Patient
GSM333448	Muscle septic k64	25	female, Age:25	Septic Patient
GSM333449	Muscle control k65	70	male, Age:70	Control Subject
GSM333450	Muscle control k66	76	male, Age:76	Control Subject
GSM333451	Muscle control k67	76	male, Age:76	Control Subject
GSM333452	Muscle control k68	72	female, Age:72	Control Subject
GSM333453	Muscle control k69	60	male, Age:60	Control Subject
GSM333454	Muscle control k70	76	male, Age:76	Control Subject
GSM333455	Muscle control k71	71	male, Age:71	Control Subject
GSM333456	Muscle control k72	70	male, Age:70	Control Subject

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