Comprehensive analysis of autophagy-related gene expression profiles identified five gene biomarkers associated with immune infiltration and advanced plaques in carotid atherosclerosis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36959587", "kind": "science-record", "revision": 4, "content_hash": "sha256:23c49dd0c08d7b162d0d71502b0e501874849a1ff554e57a68672e37a4f7625a", "created_at": "2026-11-01T19:01:36Z", "updated_at": "2026-11-01T22:51:33Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive analysis of autophagy-related gene expression profiles identified five gene biomarkers associated with immune infiltration and advanced plaques in carotid atherosclerosis.", "doi": "10.1186/s13023-023-02660-2", "pmid": "36959587", "authors": ["Chi Ma", "Taoyuan Lu", "Yanyan He", "Dehua Guo", "Lin Duan", "Rufeng Jia", "Dongyang Cai", "Tao Gao", "Zhongcan Chen", "Binghua Xue", "Tianxiao Li", "Yingkun He"], "journal": "Orphanet journal of rare diseases", "year": 2023, "abstract": "BACKGROUND: Autophagy plays an important role in the progression of carotid atherosclerosis (CAS). This study aimed to identify hub autophagy-related genes (ATGs) associated with CAS.\nMETHODS: GSE43292 and GSE28829 datasets of early and advanced CAS plaques were enrolled from the Gene Expression Omnibus (GEO) database. A comprehensive analysis of differentially expressed ATGs (DE-ATGs) was conducted. Functional enrichment assay was used to explore biological functions of DE-ATGs. The hub ATGs were identified by protein-protein interaction (PPI) network. Immunohistochemistry (IHC) and Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to validate hub ATGs at the protein level and mRNA level. Correlation analysis of hub ATGs with immune cells was also conducted. In addition, a competitive endogenous RNA (ceRNA) network was constructed, and diagnostic value of hub ATGs was evaluated.\nRESULTS: A total of 19 DE-ATGs were identified in early and advanced CAS plaques. Functional enrichment analysis of DE-ATGs suggested that they were closely correlated to autophagy, apoptosis, and lipid regulation. Moreover, 5 hub ATGs, including TNFSF10, ITGA6, CTSD, CCL2, and CASP1, were identified and further verified by IHC. The area under the curve (AUC) values of the 5 hub ATGs were 0.818, 0.732, 0.792, 0.814, and 0.812, respectively. Competing endogenous RNA (ceRNA) networks targeting the hub ATGs were also constructed. In addition, the 5 hub ATGs were found to be closely associated with immune cell infiltration in CAS.\nCONCLUSION: In this study, we identified 5 hub ATGs including CASP1, CCL2, CTSD, ITGA6 and TNFSF10, which could serve as candidate diagnostic biomarkers and therapeutic targets.", "claims": [{"id": "claim-method", "statement": "Receiver operating characteristic (ROC) curve analysis was employed to investigate the diagnostic value of these hub ATGs for discriminating advanced plaques from early plaques via “pROC” R package in GSE43292.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36959587", "locator": "sections[19] \"Diagnostic value of hub ATGs\" paragraph 2", "quote": "Receiver operating characteristic (ROC) curve analysis was employed to investigate the diagnostic value of these hub ATGs for discriminating advanced plaques from early plaques via “pROC” R package in GSE43292."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Public data used in this work can be acquired from the Gene Expression Omnibus (GEO http://www.ncbi.nlm.nih.gov/geo/). The experimental data supporting the conclusions of this article will be made available by the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36959587", "locator": "sections[29] \"Data Availability\" paragraph 2", "quote": "Public data used in this work can be acquired from the Gene Expression Omnibus (GEO http://www.ncbi.nlm.nih.gov/geo/). The experimental data supporting the conclusions of this article will be made available by the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Five autophagy-related genes—CASP1, CCL2, CTSD, ITGA6, and TNFSF10—were identified as candidate diagnostic biomarkers and therapeutic targets for carotid atherosclerosis, with respective AUC values of 0.818, 0.732, 0.792, 0.814, and 0.812.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36959587", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "In this study, we identified 5 hub ATGs including CASP1, CCL2, CTSD, ITGA6 and TNFSF10, which could serve as candidate diagnostic biomarkers and therapeutic targets."}, {"asset": "source:pmid:36959587", "locator": "sections[7] \"Diagnostic value of hub ATGs\" paragraph 2", "quote": "The values of area under the curves (AUC) of CASP1, CCL2, CTSD, ITGA6, and TNFSF10 was 0.818, 0.732, 0.792, 0.814, and 0.812, respectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Five autophagy-related genes—CASP1, CCL2, CTSD, ITGA6, and TNFSF10—were identified as candidate diagnostic biomarkers and therapeutic targets for carotid atherosclerosis, with respective AUC values of 0.818, 0.732, 0.792, 0.814, and 0.812.", "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:36959587"], "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:GSE28829"], "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:GSE28829"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36959587", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s13023-023-02660-2", "sha256": "sha256:19f97d242bd49b5ba020897228279b5b3c605dcc01b1a2713d691ee4894335db", "bytes": 47080, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s13023-023-02660-2", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10037854", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE28829", "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=GSE28829", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE28829", "version": null, "note": "Public data used in this work can be acquired from the Gene Expression Omnibus (GEO http://www.ncbi.nlm.nih.gov/geo/). 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Immunohistochemistry (IHC) and Real-time reverse transcription-qu", "raction (PPI) network. Immunohistochemistry (IHC) and Real-time reverse transcription-quantit", "SP1, were identified and further verified by IHC. The area under the curve (AUC) values of th"], "order_basis": "paper_text_order:701", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["tion-quantitative polymerase chain reaction (RT-qPCR) were used to validate hub ATGs at the prote", "n-quantitative polymerase chain reaction (RT-qPCR) were used to validate hub ATGs at the prote"], "order_basis": "paper_text_order:804", "id": "assay:2"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["t they were closely correlated to autophagy, apoptosis, and lipid regulation. Moreover, 5 hub ATGs,"], "order_basis": "paper_text_order:1257", "id": "assay:3"}, {"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": ["Receiver operating characteristic (ROC) curve analysis was employed to investigate the diagnostic value of these hub ATGs for discriminating advanced plaques from early plaques via “pROC” R package in GSE43292."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}