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pmid:37008310

Alterated gene expression in dilated cardiomyopathy after left ventricular assist device support by bioinformatics analysis.

Ying Wei · Hao Cao · Yuan-Yi Peng · Bo Zhang

Frontiers in cardiovascular medicine · 2023 doi:10.3389/fcvm.2023.1013057

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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title
Alterated gene expression in dilated cardiomyopathy after left ventricular assist device support by bioinformatics analysis.
doi
10.3389/fcvm.2023.1013057
pmid
37008310
authors array · 4 items
[0]
Ying Wei
[1]
Hao Cao
[2]
Yuan-Yi Peng
[3]
Bo Zhang
journal
Frontiers in cardiovascular medicine
year
2023
abstract
Introduction: Heart transplantation is the best treatment for end-stage dilated cardiomyopathy (DCM). Left ventricular assist device (LVAD) support is becoming more prevalent and may delay heart transplantation. Gene expression of the left ventricular myocardium usually changes following LVAD implantation. In this study, we aimed to identify potential biomarkers to determine the prognosis of patients with DCM after receiving LVAD support. Methods: We extracted microarray datasets from Gene Expression Omnibus (GEO), including GSE430 and GSE21610. There were 28 paired DCM samples in the GSE430 and GSE21610 profiles. Differentially expressed genes (DEGs) were identified at LVAD implantation and heart transplantation. DEGs were annotated according to Gene Ontology (GO) and analyzed according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. A protein-protein interaction (PPI) network was constructed. The top 10 crucial genes were predicted using Cytoscape plugin CytoHubba in conformity with the network degree algorithm. The levels of gene expression and the diagnostic values of crucial genes were confirmed in the clinical datasets. Results: The 28 DEGs were clustered into the GSE datasets. GO annotations and KEGG pathway enrichment analyses revealed that inflammation might be involved. They were associated with correlative inflammation. Combined with PPI networks, these results revealed CytoHubba's top 10 hub genes, including CCL2, CXCL12, CXCL1, CTGF/CCN2, CX3CR1, POSTN, FKBP5, SELE, AIF1, and BMP2. Among them, CCL2, CXCL12, FKBP5, and BMP2 might be considered prognostic and diagnostic biomarkers after LVAD support and have confirmed their validity in clinical datasets. The area under the curve of the four main hub genes was more than 0.85, indicating high diagnostic ability and good prognosis for patients with DCM with LVAD implantation. However, a significant effect of CCL2, CXCL12, FKBP5, and BMP2 expression was not observed on the left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), cardiac index (CI), or support time of LVAD. Conclusion: CCL2, CXCL12, FKBP5, and BMP2 could be potential gene biomarkers for patients with DCM after LVAD support. These findings provide critical clues for the therapeutic management of patients with DCM and LVADs. LVEDD, LVEF, CI, and support time of LVAD were not correlated with the expression of these hub genes.
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sections[4] "Identification of differentially expressed genes" paragraph 2
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The area under the curve of the four main hub genes was more than 0.85, indicating high diagnostic ability and good prognosis for patients with DCM with LVAD implantation.
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The area under the curve of the four main hub genes was more than 0.85, indicating high diagnostic ability and good prognosis for patients with DCM with LVAD implantation.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37008310", "kind": "science-record", "revision": 4, "content_hash": "sha256:5e7a520c753d5108c3c40351e55f12e161ccce3488d9d723db21910eaef520bc", "created_at": "2026-11-01T19:01:40Z", "updated_at": "2026-11-01T22:51:38Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Alterated gene expression in dilated cardiomyopathy after left ventricular assist device support by bioinformatics analysis.", "doi": "10.3389/fcvm.2023.1013057", "pmid": "37008310", "authors": ["Ying Wei", "Hao Cao", "Yuan-Yi Peng", "Bo Zhang"], "journal": "Frontiers in cardiovascular medicine", "year": 2023, "abstract": "Introduction: Heart transplantation is the best treatment for end-stage dilated cardiomyopathy (DCM). Left ventricular assist device (LVAD) support is becoming more prevalent and may delay heart transplantation. Gene expression of the left ventricular myocardium usually changes following LVAD implantation. In this study, we aimed to identify potential biomarkers to determine the prognosis of patients with DCM after receiving LVAD support.\nMethods: We extracted microarray datasets from Gene Expression Omnibus (GEO), including GSE430 and GSE21610. There were 28 paired DCM samples in the GSE430 and GSE21610 profiles. Differentially expressed genes (DEGs) were identified at LVAD implantation and heart transplantation. DEGs were annotated according to Gene Ontology (GO) and analyzed according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. A protein-protein interaction (PPI) network was constructed. The top 10 crucial genes were predicted using Cytoscape plugin CytoHubba in conformity with the network degree algorithm. The levels of gene expression and the diagnostic values of crucial genes were confirmed in the clinical datasets.\nResults: The 28 DEGs were clustered into the GSE datasets. GO annotations and KEGG pathway enrichment analyses revealed that inflammation might be involved. They were associated with correlative inflammation. Combined with PPI networks, these results revealed CytoHubba's top 10 hub genes, including CCL2, CXCL12, CXCL1, CTGF/CCN2, CX3CR1, POSTN, FKBP5, SELE, AIF1, and BMP2. Among them, CCL2, CXCL12, FKBP5, and BMP2 might be considered prognostic and diagnostic biomarkers after LVAD support and have confirmed their validity in clinical datasets. The area under the curve of the four main hub genes was more than 0.85, indicating high diagnostic ability and good prognosis for patients with DCM with LVAD implantation. However, a significant effect of CCL2, CXCL12, FKBP5, and BMP2 expression was not observed on the left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), cardiac index (CI), or support time of LVAD.\nConclusion: CCL2, CXCL12, FKBP5, and BMP2 could be potential gene biomarkers for patients with DCM after LVAD support. These findings provide critical clues for the therapeutic management of patients with DCM and LVADs. LVEDD, LVEF, CI, and support time of LVAD were not correlated with the expression of these hub genes.", "claims": [{"id": "claim-method", "statement": "GEO2R, an online tool (http://www.ncbi.nlm.nih.gov/geo/geo2r/) with an R-based web (R 3.2.3, Biobase 2.30.0, GEOquery 2.40.0, limma 3.26.8), was used to analyze GEO data to screen out DEGs between pre-LVAD and post-LVAD groups in the dataset.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37008310", "locator": "sections[4] \"Identification of differentially expressed genes\" paragraph 2", "quote": "GEO2R, an online tool (http://www.ncbi.nlm.nih.gov/geo/geo2r/) with an R-based web (R 3.2.3, Biobase 2.30.0, GEOquery 2.40.0, limma 3.26.8), was used to analyze GEO data to screen out DEGs between pre-LVAD and post-LVAD groups in the dataset."}], "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 in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37008310", "locator": "sections[15] \"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 in the article/Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The area under the curve of the four main hub genes was more than 0.85, indicating high diagnostic ability and good prognosis for patients with DCM with LVAD implantation.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37008310", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The area under the curve of the four main hub genes was more than 0.85, indicating high diagnostic ability and good prognosis for patients with DCM with LVAD implantation."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The area under the curve of the four main hub genes was more than 0.85, indicating high diagnostic ability and good prognosis for patients with DCM with LVAD implantation.", "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:37008310"], "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:GSE21610"], "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:GSE21610"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37008310", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcvm.2023.1013057", "sha256": "sha256:a8ef296848c4a4c30128b1baf7594d452dd932a3e06bf731ca9f4a9ae41231d1", "bytes": 27067, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fcvm.2023.1013057", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10063844", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE21610", "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=GSE21610", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE21610", "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 in the article/Supplementary Material.", "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 in the article/Supplementary Material.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM545657", "GSM545658", "GSM545659", "GSM545660", "GSM545661", "GSM545662", "GSM545663", "GSM545664", "GSM545665", "GSM545666", "GSM545667", "GSM545668", "GSM545669", "GSM545670", "GSM545671", "GSM545672", "GSM545673", "GSM545674", "GSM545675", "GSM545676", "GSM545677", "GSM545678", "GSM545679", "GSM545680", "GSM545681", "GSM545682", "GSM545683", "GSM545684", "GSM545685", "GSM545686", "GSM545687", "GSM545688", "GSM545689", "GSM545690", "GSM545691", "GSM545692", "GSM545693", "GSM545694", "GSM545695", "GSM545696", "GSM545697", "GSM545698", "GSM545699", "GSM545700", "GSM545701", "GSM545702", "GSM545703", "GSM545704", "GSM545705", "GSM545706", "GSM545707", "GSM545708", "GSM545709", "GSM545710", "GSM545711", "GSM545712", "GSM545713", "GSM545714", "GSM545715", "GSM545716", "GSM545717", "GSM545718", "GSM545719", "GSM545720", "GSM545721", "GSM545722", "GSM545723", "GSM545724"], "sample_count": 68, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Gene expression analysis in non-failing and failing myocardium pre and post pulsatile and non-pulsatile VAD support", "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:GSE430", "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=GSE430", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE430", "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 in the article/Supplementary Material.", "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 in the article/Supplementary Material.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM6540", "GSM6541", "GSM6542", "GSM6543", "GSM6545", "GSM6546", "GSM6547", "GSM6548", "GSM6549", "GSM6550", "GSM6551", "GSM6552", "GSM6553", "GSM6554"], "sample_count": 14, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Effect of left ventricular assist device support on congestive heart failure patients", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE21610 not downloaded", "asset:data:geo:GSE21610 licence not read", "asset:data:geo:GSE430 not downloaded", "asset:data:geo:GSE430 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "GEO2R, an online tool (http://www.ncbi.nlm.nih.gov/geo/geo2r/) with an R-based web (R 3.2.3, Biobase 2.30.0, GEOquery 2.40.0, limma 3.26.8), was used to analyze GEO data to screen out DEGs between pre-LVAD and post-LVAD groups in the dataset."}}, {"id": "method-2", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Student's t-test"}}, {"id": "method-3", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}, {"id": "method-4", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "pathway enrichment"}}, {"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": [], "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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"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": {"tier": "R1", "reachable": true, "accessions": ["GSE430", "GSE21610"], "resolved_accessions": ["GSE430", "GSE21610"], "statements": ["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 in the article/Supplementary Material."], "basis": "The paper names GSE430, GSE21610 in National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:37008310", "data:geo:GSE21610"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE21610"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:35:38Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 7691, "completion_tokens": 1614, "cached_tokens": 188}}, "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:37008310", "type": "paper", "label": "pmid:37008310"}, {"id": "source:pmid:37008310", "type": "manuscript", "label": "PMID 37008310 full text"}, {"id": "data:geo:GSE21610", "type": "dataset", "label": "GEO GSE21610"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37008310", "type": "paper", "label": "pmid:37008310"}, {"id": "source:pmid:37008310", "type": "manuscript", "label": "PMID 37008310 full text"}, {"id": "data:geo:GSE21610", "type": "dataset", "label": "GEO GSE21610"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37008310", "type": "extraction", "used": ["source:pmid:37008310"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE21610", "type": "accession_resolution", "used": ["data:geo:GSE21610"], "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:37008310", "parent_hash": "sha256:628de05dc66307fc0ddbe1cdd2fabd868031fe49f2ac012e6ba4b2821ad9cb43", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE21610 licence not read", "asset:data:geo:GSE21610 not downloaded", "asset:data:geo:GSE430 licence not read", "asset:data:geo:GSE430 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": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["eceiving LVAD support. Methods: We extracted microarray datasets from Gene Expression Omnibus (GEO),"], "order_basis": "paper_text_order:545", "id": "assay:1"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["GEO2R, an online tool (http://www.ncbi.nlm.nih.gov/geo/geo2r/) with an R-based web (R 3.2.3, Biobase 2.30.0, GEOquery 2.40.0, limma 3.26.8), was used to analyze GEO data to screen out DEGs between pre-LVAD and post-LVAD groups in the dataset."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}