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pmid:36247429

The relationship between soluble lymphocyte activation gene-3 and coronary artery disease.

Xinlin Xiong · Zonggang Duan · Haiyan Zhou · Li Niu · Zhenhua Luo · Wei Li

Frontiers in cardiovascular medicine · 2022 doi:10.3389/fcvm.2022.988582

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

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title
The relationship between soluble lymphocyte activation gene-3 and coronary artery disease.
doi
10.3389/fcvm.2022.988582
pmid
36247429
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[0]
Xinlin Xiong
[1]
Zonggang Duan
[2]
Haiyan Zhou
[3]
Li Niu
[4]
Zhenhua Luo
[5]
Wei Li
journal
Frontiers in cardiovascular medicine
year
2022
abstract
Background: Soluble lymphocyte activation gene 3 (sLAG3) may be used for diagnosis or prognosis in various diseases. However, the relationship between sLAG3 and coronary artery disease (CAD) are still unclear. This study aimed to investigate the levels of sLAG3 in patients with CAD, and its potential clinical association with the disease. Methods: A total of 66 subjects (49 patients with CAD and 17 control subjects without CAD) were enrolled. The sLAG3 level was measured using enzyme-linked immunosorbent assay (ELISA) kits. Clinical variables included demographics, biochemical markers, coronary angiography status, and ejection fraction of the heart (EF) were collected, and Gensini scores were calculated. LAG3 gene data was extracted from three datasets (GSE23561, GSE61144, GSE60993) in Gene Expression Omnibus (GEO) to compare differential expression between CAD and control subjects. Results: The sLAG3 level was significantly lower in the CAD vs. the controls (P < 0.05), and negatively associated with CAD [odds ratio (OR): 0.212, 95% confidential interval (CI): 0.060-0.746, P < 0.05]. Furthermore, the area under the curve (AUC) of sLAG3 level was significant (P < 0.05). The sLAG3 level in subjects with body mass index (BMI) ≥ 24 kg/m2 was lower compared to those with BMI < 24 kg/m2 (P < 0.05). The sLAG3 level was also negatively associated with BMI and diabetes mellitus (P < 0.05), though not associated with the Gensini scores or EF (P > 0.05). Lastly, the LAG3 gene expression in peripheral whole blood of patients with CAD were down-regulated compared to healthy controls (P < 0.05). Conclusion: The sLAG3 level was negatively associated with the occurrence but not severity of CAD. Meanwhile, the sLAG3 was negatively associated with BMI and diabetes mellitus, suggesting the reduced sLAG3 might be a novel risk factor for developing CAD.
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Logistic regression analyses were performed to identify associations of sLAG3 with CAD in different regression models.
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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/, GSE23561, GSE60993, and GSE61144.
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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/, GSE23561, GSE60993, and GSE61144.
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Reduced soluble lymphocyte activation gene 3 levels were associated with the occurrence, but not the severity, of coronary artery disease.
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The sLAG3 level was significantly lower in the CAD vs. the controls (P < 0.05), and negatively associated with CAD [odds ratio (OR): 0.212, 95% confidential interval (CI): 0.060–0.746, P < 0.05].
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The sLAG3 level was significantly lower in the CAD vs. the controls (P < 0.05), and negatively associated with CAD [odds ratio (OR): 0.212, 95% confidential interval (CI): 0.060–0.746, P < 0.05].
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The sLAG3 level was also negatively associated with BMI and diabetes mellitus (P < 0.05), though not associated with the Gensini scores or EF (P > 0.05).
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Reduced soluble lymphocyte activation gene 3 levels were associated with the occurrence, but not the severity, of coronary artery disease.
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36247429", "kind": "science-record", "revision": 4, "content_hash": "sha256:0c27884d55d4441a711adbeea36e2126f95380bbf4a765c4ccb4dda8ba1aabe1", "created_at": "2026-11-01T18:15:38Z", "updated_at": "2026-11-01T22:07:52Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The relationship between soluble lymphocyte activation gene-3 and coronary artery disease.", "doi": "10.3389/fcvm.2022.988582", "pmid": "36247429", "authors": ["Xinlin Xiong", "Zonggang Duan", "Haiyan Zhou", "Li Niu", "Zhenhua Luo", "Wei Li"], "journal": "Frontiers in cardiovascular medicine", "year": 2022, "abstract": "Background: Soluble lymphocyte activation gene 3 (sLAG3) may be used for diagnosis or prognosis in various diseases. However, the relationship between sLAG3 and coronary artery disease (CAD) are still unclear. This study aimed to investigate the levels of sLAG3 in patients with CAD, and its potential clinical association with the disease.\nMethods: A total of 66 subjects (49 patients with CAD and 17 control subjects without CAD) were enrolled. The sLAG3 level was measured using enzyme-linked immunosorbent assay (ELISA) kits. Clinical variables included demographics, biochemical markers, coronary angiography status, and ejection fraction of the heart (EF) were collected, and Gensini scores were calculated. LAG3 gene data was extracted from three datasets (GSE23561, GSE61144, GSE60993) in Gene Expression Omnibus (GEO) to compare differential expression between CAD and control subjects.\nResults: The sLAG3 level was significantly lower in the CAD vs. the controls (P < 0.05), and negatively associated with CAD [odds ratio (OR): 0.212, 95% confidential interval (CI): 0.060-0.746, P < 0.05]. Furthermore, the area under the curve (AUC) of sLAG3 level was significant (P < 0.05). The sLAG3 level in subjects with body mass index (BMI) ≥ 24 kg/m2 was lower compared to those with BMI < 24 kg/m2 (P < 0.05). The sLAG3 level was also negatively associated with BMI and diabetes mellitus (P < 0.05), though not associated with the Gensini scores or EF (P > 0.05). Lastly, the LAG3 gene expression in peripheral whole blood of patients with CAD were down-regulated compared to healthy controls (P < 0.05).\nConclusion: The sLAG3 level was negatively associated with the occurrence but not severity of CAD. Meanwhile, the sLAG3 was negatively associated with BMI and diabetes mellitus, suggesting the reduced sLAG3 might be a novel risk factor for developing CAD.", "claims": [{"id": "claim-method", "statement": "Logistic regression analyses were performed to identify associations of sLAG3 with CAD in different regression models.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36247429", "locator": "sections[7] \"Statistical analysis\" paragraph 2", "quote": "Logistic regression analyses were performed to identify associations of sLAG3 with CAD in different regression models."}], "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/, GSE23561, GSE60993, and GSE61144.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36247429", "locator": "sections[18] \"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/, GSE23561, GSE60993, and GSE61144."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Reduced soluble lymphocyte activation gene 3 levels were associated with the occurrence, but not the severity, of coronary artery disease.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "The sLAG3 level was significantly lower in the CAD vs. the controls (P < 0.05), and negatively associated with CAD [odds ratio (OR): 0.212, 95% confidential interval (CI): 0.060–0.746, P < 0.05]."}, "evidence": [{"asset": "source:pmid:36247429", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The sLAG3 level was significantly lower in the CAD vs. the controls (P < 0.05), and negatively associated with CAD [odds ratio (OR): 0.212, 95% confidential interval (CI): 0.060–0.746, P < 0.05]."}, {"asset": "source:pmid:36247429", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The sLAG3 level was also negatively associated with BMI and diabetes mellitus (P < 0.05), though not associated with the Gensini scores or EF (P > 0.05)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Reduced soluble lymphocyte activation gene 3 levels were associated with the occurrence, but not the severity, of coronary artery disease.", "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:36247429"], "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:GSE23561"], "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:GSE23561"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36247429", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcvm.2022.988582", "sha256": "sha256:b81709a6b50982a9a6c0754d8844b0f33ef0de887517a6c0a42ecade7eac91ee", "bytes": 34570, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fcvm.2022.988582", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9558825", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE23561", "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=GSE23561", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE23561", "version": null, "note": "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/, GSE23561, GSE60993, and GSE61144.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "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/, GSE23561, GSE60993, and GSE61144.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM577963", "GSM577964", "GSM577965", "GSM577966", "GSM577967", "GSM577968", "GSM577969", "GSM577970", "GSM577971", "GSM577972", "GSM577973", "GSM577974", "GSM577975", "GSM577976", "GSM577977", "GSM577978", "GSM577979", "GSM577980", "GSM577981", "GSM577982", "GSM577983", "GSM577984", "GSM577985", "GSM577986", "GSM577987", "GSM577988", "GSM577989", "GSM577990", "GSM577991", "GSM577992", "GSM577993", "GSM577994", "GSM577995", "GSM577996", "GSM577997"], "sample_count": 35, "group_sizes": null, "group_sizes_basis": null, "platform": "10775", "taxon": "Homo sapiens", "title": "Peripheral blood gene expression profiles in metabolic syndrome, coronary artery disease and type 2 diabetes", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE60993", "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=GSE60993", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE60993", "version": null, "note": "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/, GSE23561, GSE60993, and GSE61144.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "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/, GSE23561, GSE60993, and GSE61144.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1495313", "GSM1495314", "GSM1495315", "GSM1495316", "GSM1495317", "GSM1495318", "GSM1495319", "GSM1495320", "GSM1495321", "GSM1495322", "GSM1495323", "GSM1495324", "GSM1495325", "GSM1495326", "GSM1495327", "GSM1495328", "GSM1495329", "GSM1495330", "GSM1495331", "GSM1495332", "GSM1495333", "GSM1495334", "GSM1495335", "GSM1495336", "GSM1495337", "GSM1495338", "GSM1495339", "GSM1495340", "GSM1495341", "GSM1495342", "GSM1495343", "GSM1495344", "GSM1495345"], "sample_count": 33, "group_sizes": null, "group_sizes_basis": null, "platform": "6884", "taxon": "Homo sapiens", "title": "Assessment and Diagnostic Relevance of Novel Serum Biomarkers for Early Decision of ST-elevation Myocardial Infarction", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE23561 not downloaded", "asset:data:geo:GSE23561 licence not read", "asset:data:geo:GSE60993 not downloaded", "asset:data:geo:GSE60993 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "regression_modelling", "specific": "logistic", "label": "Regression modelling", "dsl_operations": ["glm_logit_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["predictors_and_outcome"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Logistic regression analyses were performed to identify associations of sLAG3 with CAD in different regression models."}}, {"id": "method-2", "family": "group_comparison", "specific": "mann_whitney", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_mann_whitney"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Mann-Whitney"}}, {"id": "method-3", "family": "principal_component_analysis", "specific": "pca", "label": "Principal component analysis", "dsl_operations": ["pca_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["wide_numeric_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "Principal component analysis"}}, {"id": "method-4", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.8, "band": "high", "quote": "ROC curve"}}, {"id": "method-5", "family": "contingency_analysis", "specific": "chi_square", "label": "Categorical (contingency table) analysis", "dsl_operations": ["chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.8, "band": "high", "quote": "chi-square"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "chi_square_test", "expected_value": 95.0, "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."}, {"id": "target-published-estimate-p-value", "claim_id": "claim-target-result", "operation": "chi_square_test", "expected_value": 0.05, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold."}], "gaps": ["method.reader_differs_from_extractor"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["glm_logit_fit"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: logistic."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["glm_logit_fit"], "assets": ["source:pmid:36247429", "data:geo:GSE23561"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE23561"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:11:18Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 10890, "completion_tokens": 1782, "cached_tokens": 256}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:36247429", "type": "paper", "label": "pmid:36247429"}, {"id": "source:pmid:36247429", "type": "manuscript", "label": "PMID 36247429 full text"}, {"id": "data:geo:GSE23561", "type": "dataset", "label": "GEO GSE23561"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36247429", "type": "paper", "label": "pmid:36247429"}, {"id": "source:pmid:36247429", "type": "manuscript", "label": "PMID 36247429 full text"}, {"id": "data:geo:GSE23561", "type": "dataset", "label": "GEO GSE23561"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36247429", "type": "extraction", "used": ["source:pmid:36247429"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE23561", "type": "accession_resolution", "used": ["data:geo:GSE23561"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:36247429", "parent_hash": "sha256:7445b12c983bc31250dd3028e56faf3f35e31221a0b56e0229b807be58086987", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE23561 licence not read", "asset:data:geo:GSE23561 not downloaded", "asset:data:geo:GSE60993 licence not read", "asset:data:geo:GSE60993 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "elisa", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["red using enzyme-linked immunosorbent assay (ELISA) kits. 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