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pmid:34785936

Identification and Validation of Autophagy-Related Genes as Potential Biomarkers and Therapeutic Targets in Atrial Fibrillation.

Jiao Zhou · Yunlong Dong · Xiang Cai · Hongbo Yang · Tao Guo

International journal of general medicine · 2021 doi:10.2147/IJGM.S337855

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Experiment

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Data

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Identification and Validation of Autophagy-Related Genes as Potential Biomarkers and Therapeutic Targets in Atrial Fibrillation.
doi
10.2147/IJGM.S337855
pmid
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Jiao Zhou
[1]
Yunlong Dong
[2]
Xiang Cai
[3]
Hongbo Yang
[4]
Tao Guo
journal
International journal of general medicine
year
2021
abstract
BACKGROUND: Autophagy is an evolutionary conserved important process for the turnover of intracellular substances in eukaryotes and is closely related to the development of atrial fibrillation (AF). The aim of this study is to identify and validate potential autophagy-related genes (ARGs) of AF through bioinformatics analysis and experimental validation. METHODS: We downloaded two data sets from the Gene Expression Omnibus (GEO) database, GSE14975 and GSE31821. After merging the data of the two microarrays, adjusting the batch effect, and integrating the differentially expressed genes (DEGs) with ARGs to obtain differentially expressed autophagy-related genes (DEARGs). Functional and pathway enrichment analyses were carried out based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Use the STRING database to construct a protein-protein interaction (PPI) network. Finally, mRNA expression levels of DEARGs were validated in right atrial tissue samples from AF patients and non-AF controls by qRT-PCR. RESULTS: Through bioinformatics analysis, we finally identified 11 DEARGs (CDKN1A, CXCR4, DIRAS3, HSP90AB1, ITGA3, PRKCD, TP53INP2, DAPK2, IFNG, PTK6, and TNFSF10) in AF using [log2 (fold change)] > 0.5 and P < 0.05. In the pathway enrichment analysis, the most significantly enriched pathway was the autophagy pathway. The results of validation showed that the expression levels of CXCR4, DAPK2, and TNFSF10 corroborating with our computational findings, and the results were statistically significant (P<0.05). CONCLUSION: Our study demonstrates that these 11 potential crucial ARGs, especially CXCR4, DAPK2, and TNFSF10, may be potential biomarkers and therapeutic targets in AF, which will help the personalized treatment of AF patients.
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The DEGs were screened with R software limma package version 3.44.3 (http://bioconductor.org/packages/release/bioc/html/limma.html) under the criteria of [log2 (fold change)] >0.5 and P <0.05.
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The DEGs were screened with R software limma package version 3.44.3 (http://bioconductor.org/packages/release/bioc/html/limma.html) under the criteria of [log2 (fold change)] >0.5 and P <0.05.
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The merged GEO microarray analysis identified 11 differentially expressed autophagy-related genes in atrial fibrillation, with CXCR4, DAPK2, and TNFSF10 subsequently corroborated by qRT-PCR.
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Through bioinformatics analysis, we finally identified 11 DEARGs (CDKN1A, CXCR4, DIRAS3, HSP90AB1, ITGA3, PRKCD, TP53INP2, DAPK2, IFNG, PTK6, and TNFSF10) in AF using [log2 (fold change)] > 0.5 and P < 0.05.
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Through bioinformatics analysis, we finally identified 11 DEARGs (CDKN1A, CXCR4, DIRAS3, HSP90AB1, ITGA3, PRKCD, TP53INP2, DAPK2, IFNG, PTK6, and TNFSF10) in AF using [log2 (fold change)] > 0.5 and P < 0.05.
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The results of validation showed that the expression levels of CXCR4, DAPK2, and TNFSF10 corroborating with our computational findings, and the results were statistically significant (P<0.05).
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The merged GEO microarray analysis identified 11 differentially expressed autophagy-related genes in atrial fibrillation, with CXCR4, DAPK2, and TNFSF10 subsequently corroborated by qRT-PCR.
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Rac1-Induced Connective Tissue Growth Factor regulates Connexin 43 and N-Cadherin Expression in Atrial Fibrillation
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34785936", "kind": "science-record", "revision": 5, "content_hash": "sha256:e897e329c7093f3687394e86df952edad6f25edf1a7fe803be73f61f51eacc67", "created_at": "2026-11-01T17:36:29Z", "updated_at": "2026-11-01T22:47:53Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and Validation of Autophagy-Related Genes as Potential Biomarkers and Therapeutic Targets in Atrial Fibrillation.", "doi": "10.2147/IJGM.S337855", "pmid": "34785936", "authors": ["Jiao Zhou", "Yunlong Dong", "Xiang Cai", "Hongbo Yang", "Tao Guo"], "journal": "International journal of general medicine", "year": 2021, "abstract": "BACKGROUND: Autophagy is an evolutionary conserved important process for the turnover of intracellular substances in eukaryotes and is closely related to the development of atrial fibrillation (AF). The aim of this study is to identify and validate potential autophagy-related genes (ARGs) of AF through bioinformatics analysis and experimental validation.\nMETHODS: We downloaded two data sets from the Gene Expression Omnibus (GEO) database, GSE14975 and GSE31821. After merging the data of the two microarrays, adjusting the batch effect, and integrating the differentially expressed genes (DEGs) with ARGs to obtain differentially expressed autophagy-related genes (DEARGs). Functional and pathway enrichment analyses were carried out based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Use the STRING database to construct a protein-protein interaction (PPI) network. Finally, mRNA expression levels of DEARGs were validated in right atrial tissue samples from AF patients and non-AF controls by qRT-PCR.\nRESULTS: Through bioinformatics analysis, we finally identified 11 DEARGs (CDKN1A, CXCR4, DIRAS3, HSP90AB1, ITGA3, PRKCD, TP53INP2, DAPK2, IFNG, PTK6, and TNFSF10) in AF using [log2 (fold change)] > 0.5 and P < 0.05. In the pathway enrichment analysis, the most significantly enriched pathway was the autophagy pathway. The results of validation showed that the expression levels of CXCR4, DAPK2, and TNFSF10 corroborating with our computational findings, and the results were statistically significant (P<0.05).\nCONCLUSION: Our study demonstrates that these 11 potential crucial ARGs, especially CXCR4, DAPK2, and TNFSF10, may be potential biomarkers and therapeutic targets in AF, which will help the personalized treatment of AF patients.", "claims": [{"id": "claim-method", "statement": "The DEGs were screened with R software limma package version 3.44.3 (http://bioconductor.org/packages/release/bioc/html/limma.html) under the criteria of [log2 (fold change)] >0.5 and P <0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34785936", "locator": "sections[4] \"Screening of Differentially Expressed Genes (DEGs)\" paragraph 2", "quote": "The DEGs were screened with R software limma package version 3.44.3 (http://bioconductor.org/packages/release/bioc/html/limma.html) under the criteria of [log2 (fold change)] >0.5 and P <0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data analyzed in the present study can be accessed on the GEO (https://www.ncbi.nlm.nih.gov/geo/) website.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34785936", "locator": "sections[23] \"Data Sharing Statement\" paragraph 2", "quote": "The data analyzed in the present study can be accessed on the GEO (https://www.ncbi.nlm.nih.gov/geo/) website."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The merged GEO microarray analysis identified 11 differentially expressed autophagy-related genes in atrial fibrillation, with CXCR4, DAPK2, and TNFSF10 subsequently corroborated by qRT-PCR.", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "Through bioinformatics analysis, we finally identified 11 DEARGs (CDKN1A, CXCR4, DIRAS3, HSP90AB1, ITGA3, PRKCD, TP53INP2, DAPK2, IFNG, PTK6, and TNFSF10) in AF using [log2 (fold change)] > 0.5 and P < 0.05."}, "evidence": [{"asset": "source:pmid:34785936", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Through bioinformatics analysis, we finally identified 11 DEARGs (CDKN1A, CXCR4, DIRAS3, HSP90AB1, ITGA3, PRKCD, TP53INP2, DAPK2, IFNG, PTK6, and TNFSF10) in AF using [log2 (fold change)] > 0.5 and P < 0.05."}, {"asset": "source:pmid:34785936", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The results of validation showed that the expression levels of CXCR4, DAPK2, and TNFSF10 corroborating with our computational findings, and the results were statistically significant (P<0.05)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The merged GEO microarray analysis identified 11 differentially expressed autophagy-related genes in atrial fibrillation, with CXCR4, DAPK2, and TNFSF10 subsequently corroborated by qRT-PCR.", "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:34785936"], "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:GSE14975"], "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:GSE14975"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34785936", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/IJGM.S337855", "sha256": "sha256:5c177bfcba8ee1023e92b2f53f2247982b6403551d7d9b0f06c8f3317b93d887", "bytes": 35166, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/IJGM.S337855", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8580288", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE14975", "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=GSE14975", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE14975", "version": null, "note": "The data analyzed in the present study can be accessed on the GEO (https://www.ncbi.nlm.nih.gov/geo/) website.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data analyzed in the present study can be accessed on the GEO (https://www.ncbi.nlm.nih.gov/geo/) website.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM373956", "GSM373957", "GSM373958", "GSM373959", "GSM373960", "GSM373961", "GSM373962", "GSM373963", "GSM373964", "GSM373965"], "sample_count": 10, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Rac1-Induced Connective Tissue Growth Factor regulates Connexin 43 and N-Cadherin Expression in Atrial Fibrillation", "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:GSE31821", "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=GSE31821", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE31821", "version": null, "note": "The data analyzed in the present study can be accessed on the GEO (https://www.ncbi.nlm.nih.gov/geo/) website.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data analyzed in the present study can be accessed on the GEO (https://www.ncbi.nlm.nih.gov/geo/) website.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM789270", "GSM789271", "GSM789272", "GSM789273", "GSM789274", "GSM789275"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Gene expression and miRNA profiles in atrial fibrillation. 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A run that reproduces the effect is judged against this threshold."}], "gaps": []}, "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": ["GSE14975", "GSE31821"], "resolved_accessions": ["GSE14975", "GSE31821"], "statements": ["The data analyzed in the present study can be accessed on the GEO (https://www.ncbi.nlm.nih.gov/geo/) website."], "basis": "The paper names GSE14975, GSE31821 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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