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pmid:36684561

Immune-related potential biomarkers and therapeutic targets in coronary artery disease.

Chaosheng Liu · Jifeng Liu · Yunshu Zhang · Xi Wang · Yue Guan

Frontiers in cardiovascular medicine · 2022 doi:10.3389/fcvm.2022.1055422

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complete

Experiment

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Data

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Analysis

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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title
Immune-related potential biomarkers and therapeutic targets in coronary artery disease.
doi
10.3389/fcvm.2022.1055422
pmid
36684561
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[0]
Chaosheng Liu
[1]
Jifeng Liu
[2]
Yunshu Zhang
[3]
Xi Wang
[4]
Yue Guan
journal
Frontiers in cardiovascular medicine
year
2022
abstract
Background: Coronary artery disease (CAD) is a complex illness with unknown pathophysiology. Peripheral biomarkers are a non-invasive method required to track the onset and progression of CAD and have unbeatable benefits in terms of early identification, prognostic assessment, and categorization of the diagnosis. This study aimed to identify and validate the diagnostic and therapeutic potential of differentially expressed immune-related genes (DE-IRGs) in CAD, which will aid in improving our knowledge on the etiology of CAD and in forming genetic predictions. Methods: First, we searched coronary heart disease in the Gene Expression Omnibus (GEO) database and identified GSE20680 (CAD = 87, Normal = 52) as the trial set and GSE20681 (CAD = 99, Normal = 99) as the validation set. Functional enrichment analysis using protein-protein interactions (PPIs), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) was carried out on the identified differentially expressed genes. Optimal feature genes (OFGs) were generated using the support vector machine recursive feature elimination algorithm and the least absolute shrinkage and selection operator (LASSO) algorithm. Furthermore, immune infiltration in CAD patients and healthy controls was compared using CIBERSORT, and the relationship between immune cells and OFGs was examined. In addition, we constructed potential targeted drugs for this model through the Drug-Gene Interaction database (DGIdb) database. Finally, we verify the expression of S100A8-dominated OFGs in the GSE20681 dataset to confirm the universality of our study. Results: We identified the ten best OFGs for CAD from the DE-IRGs. Functional enrichment analysis showed that these marker genes are crucial for receptor-ligand activity, signaling receptor activator activity, and positive control of the response to stimuli from the outside world. Additionally, CIBERSORT revealed that S100A8 could be connected to alterations in the immune microenvironment in CAD patients. Furthermore, with the help of DGIdb and Cytoscape, a total of 64 medicines that target five marker genes were subsequently discovered. Finally, we verified the expression of the OFGs genes in the GSE20681 dataset between CAD patients and normal patients and found that there was also a significant difference in the expression of S100A8. Conclusion: We created a 10-gene immune-related prognostic model for CAD and confirmed its validity. The model can identify potential biomarkers for CAD prediction and more accurately gauge the progression of the disease.
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We screened for DE-IRGs between CAD and controls using the “LIMMA” package in the R software using the combined datasets (P < 0.05).
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sections[4] "2.2. Identification of DE-IRGs" paragraph 2
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We screened for DE-IRGs between CAD and controls using the “LIMMA” package in the R software using the combined datasets (P < 0.05).
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The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/geo/, GSE20680 and https://www.ncbi.nlm.nih.gov/geo/, GSE20681.
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The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/geo/, GSE20680 and https://www.ncbi.nlm.nih.gov/geo/, GSE20681.
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Using the “glm” package, we created a logistic regression model based on the 10 OFGs mentioned above, which could distinguish between normal and CAD samples with an AUC of 0.889 [95% confidence interval (CI): 0.830–0.938], according to the ROC curve (Figure 3F).
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Using the “glm” package, we created a logistic regression model based on the 10 OFGs mentioned above, which could distinguish between normal and CAD samples with an AUC of 0.889 [95% confidence interval (CI): 0.830–0.938], according to the ROC curve (Figure 3F).
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sections[13] "3.3. Identification of OFGs for CAD" paragraph 4
quote
Using the “glm” package, we created a logistic regression model based on the 10 OFGs mentioned above, which could distinguish between normal and CAD samples with an AUC of 0.889 [95% confidence interval (CI): 0.830–0.938], according to the ROC curve (Figure 3F).
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Using the “glm” package, we created a logistic regression model based on the 10 OFGs mentioned above, which could distinguish between normal and CAD samples with an AUC of 0.889 [95% confidence interval (CI): 0.830–0.938], according to the ROC curve (Figure 3F).
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Whole Blood Cell Gene Expression Profiling in Patients with Coronary Artery Disease from the Cathgen Registry
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complete
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method-1
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Differential expression analysis
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[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
count_matrix_with_condition
evidence object · 3 fields
score
1
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verbatim
quote
We screened for DE-IRGs between CAD and controls using the “LIMMA” package in the R software using the combined datasets (P < 0.05).
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machine_learning
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dsl_operations array · 3 items
[0]
train_classifier
[1]
cross_validate
[2]
roc_auc
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
labelled_feature_matrix
evidence object · 3 fields
score
0.7
band
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quote
support vector machine
[2] object · 10 fields
id
method-3
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correlation_analysis
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pearson
label
Correlation analysis
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pearson_r
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
paired_numeric_columns
evidence object · 3 fields
score
0.8
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high
quote
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id
method-4
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network_analysis
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label
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[0]
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[1]
centrality_scores
[2]
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missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
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evidence object · 3 fields
score
0.7
band
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PPI
[4] object · 10 fields
id
method-5
family
network_analysis
specific
pathway_enrichment
label
Network / pathway analysis
dsl_operations array · 1 item
[0]
pathway_enrich
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
edge_list
evidence object · 3 fields
score
0.8
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quote
pathway enrichment
targets array · 2 items
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id
target-published-estimate
claim_id
claim-target-result
operation
build_graph
unit
per cent
tolerance
null
state
complete
note
The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none.
[1] object · 8 fields
id
target-published-estimate-auc
claim_id
claim-target-result
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build_graph
unit
auc
tolerance
null
state
complete
note
The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none.
gaps array · 0 items
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
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assay_families array · 9 items
[0]
meta_analysis
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[4]
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[5]
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[6]
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[7]
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[8]
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candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
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blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
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true
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[1]
differential_expression_fit
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fdr_bh
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basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
reachable
true
accessions array · 2 items
[0]
GSE20680
[1]
GSE20681
resolved_accessions array · 2 items
[0]
GSE20680
[1]
GSE20681
statements array · 1 item
[0]
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/geo/, GSE20680 and https://www.ncbi.nlm.nih.gov/geo/, GSE20681.
basis
The paper names GSE20680, GSE20681 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
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[2]
fdr_bh
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source:pmid:36684561
[1]
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steps array · 1 item
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run_analysis
must_build object · 5 fields
dsl_operations array · 0 items
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readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
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data:geo:GSE20680
gaps array · 0 items
review object · 5 fields
state
partial
machine_critique object · 5 fields
kind
extraction_review
reader object · 5 fields
model
MiniMax-M3.1-Flash
provider
minimax
provider_family
minimax
read_at
2026-11-01T18:24:05Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
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5
usage object · 3 fields
prompt_tokens
12614
completion_tokens
1693
cached_tokens
256
stages array · 1 item
[0] object · 4 fields
id
extraction
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complete
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MiniMax-M3.1-Flash
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minimax
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[1]
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[2]
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absent
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provenance object · 7 fields
entities array · 3 items
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pmid:36684561
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paper
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pmid:36684561
[1] object · 3 fields
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source:pmid:36684561
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manuscript
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PMID 36684561 full text
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data:geo:GSE20680
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dataset
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GEO GSE20680
activities array · 3 items
[0] object · 4 fields
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activity-reading-sci-2026-11-01
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paper
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pmid:36684561
[1] object · 3 fields
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source:pmid:36684561
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manuscript
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PMID 36684561 full text
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data:geo:GSE20680
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dataset
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GEO GSE20680
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agent:corpus-assay-engine
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agent:minimax-reader
[2] object · 4 fields
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activity-resolve-GSE20680
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accession_resolution
used array · 1 item
[0]
data:geo:GSE20680
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agent:corpus-assay-engine
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[0] object · 3 fields
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MiniMax literature reader
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343fb30756ba6ec3
capability_table_fingerprint
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asset:data:geo:GSE20680 licence not read
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[6]
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role
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[2]
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supported
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dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
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We screened for DE-IRGs between CAD and controls using the “LIMMA” package in the R software using the combined datasets (P < 0.05).
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36684561", "kind": "science-record", "revision": 4, "content_hash": "sha256:e2dbb6533fccaba9a96238b74062ac58391869a17b02299358d947e54b8883ac", "created_at": "2026-11-01T19:01:13Z", "updated_at": "2026-11-01T22:51:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Immune-related potential biomarkers and therapeutic targets in coronary artery disease.", "doi": "10.3389/fcvm.2022.1055422", "pmid": "36684561", "authors": ["Chaosheng Liu", "Jifeng Liu", "Yunshu Zhang", "Xi Wang", "Yue Guan"], "journal": "Frontiers in cardiovascular medicine", "year": 2022, "abstract": "Background: Coronary artery disease (CAD) is a complex illness with unknown pathophysiology. Peripheral biomarkers are a non-invasive method required to track the onset and progression of CAD and have unbeatable benefits in terms of early identification, prognostic assessment, and categorization of the diagnosis. This study aimed to identify and validate the diagnostic and therapeutic potential of differentially expressed immune-related genes (DE-IRGs) in CAD, which will aid in improving our knowledge on the etiology of CAD and in forming genetic predictions.\nMethods: First, we searched coronary heart disease in the Gene Expression Omnibus (GEO) database and identified GSE20680 (CAD = 87, Normal = 52) as the trial set and GSE20681 (CAD = 99, Normal = 99) as the validation set. Functional enrichment analysis using protein-protein interactions (PPIs), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) was carried out on the identified differentially expressed genes. Optimal feature genes (OFGs) were generated using the support vector machine recursive feature elimination algorithm and the least absolute shrinkage and selection operator (LASSO) algorithm. Furthermore, immune infiltration in CAD patients and healthy controls was compared using CIBERSORT, and the relationship between immune cells and OFGs was examined. In addition, we constructed potential targeted drugs for this model through the Drug-Gene Interaction database (DGIdb) database. Finally, we verify the expression of S100A8-dominated OFGs in the GSE20681 dataset to confirm the universality of our study.\nResults: We identified the ten best OFGs for CAD from the DE-IRGs. Functional enrichment analysis showed that these marker genes are crucial for receptor-ligand activity, signaling receptor activator activity, and positive control of the response to stimuli from the outside world. Additionally, CIBERSORT revealed that S100A8 could be connected to alterations in the immune microenvironment in CAD patients. Furthermore, with the help of DGIdb and Cytoscape, a total of 64 medicines that target five marker genes were subsequently discovered. Finally, we verified the expression of the OFGs genes in the GSE20681 dataset between CAD patients and normal patients and found that there was also a significant difference in the expression of S100A8.\nConclusion: We created a 10-gene immune-related prognostic model for CAD and confirmed its validity. The model can identify potential biomarkers for CAD prediction and more accurately gauge the progression of the disease.", "claims": [{"id": "claim-method", "statement": "We screened for DE-IRGs between CAD and controls using the “LIMMA” package in the R software using the combined datasets (P < 0.05).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36684561", "locator": "sections[4] \"2.2. Identification of DE-IRGs\" paragraph 2", "quote": "We screened for DE-IRGs between CAD and controls using the “LIMMA” package in the R software using the combined datasets (P < 0.05)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/geo/, GSE20680 and https://www.ncbi.nlm.nih.gov/geo/, GSE20681.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36684561", "locator": "sections[20] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/geo/, GSE20680 and https://www.ncbi.nlm.nih.gov/geo/, GSE20681."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using the “glm” package, we created a logistic regression model based on the 10 OFGs mentioned above, which could distinguish between normal and CAD samples with an AUC of 0.889 [95% confidence interval (CI): 0.830–0.938], according to the ROC curve (Figure 3F).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Using the “glm” package, we created a logistic regression model based on the 10 OFGs mentioned above, which could distinguish between normal and CAD samples with an AUC of 0.889 [95% confidence interval (CI): 0.830–0.938], according to the ROC curve (Figure 3F)."}, "evidence": [{"asset": "source:pmid:36684561", "locator": "sections[13] \"3.3. Identification of OFGs for CAD\" paragraph 4", "quote": "Using the “glm” package, we created a logistic regression model based on the 10 OFGs mentioned above, which could distinguish between normal and CAD samples with an AUC of 0.889 [95% confidence interval (CI): 0.830–0.938], according to the ROC curve (Figure 3F)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using the “glm” package, we created a logistic regression model based on the 10 OFGs mentioned above, which could distinguish between normal and CAD samples with an AUC of 0.889 [95% confidence interval (CI): 0.830–0.938], according to the ROC curve (Figure 3F).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36684561"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE20680"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE20680"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36684561", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcvm.2022.1055422", "sha256": "sha256:c43f41f4b955b7bb6408ff65195521d2fbc3e597cf3fda4407fc47317e474304", "bytes": 43562, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fcvm.2022.1055422", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9853173", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE20680", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE20680", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE20680", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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