Role of Necroptosis and Immune Infiltration in Human Stanford Type A Aortic Dissection: Novel Insights from Bioinformatics Analyses.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35480868", "kind": "science-record", "revision": 4, "content_hash": "sha256:3c9003abb636d1ae0655f817c6ae6bc9cee43b5f9b4fd3fafa5ad079c3d45362", "created_at": "2026-11-01T18:14:21Z", "updated_at": "2026-11-01T22:06:24Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Role of Necroptosis and Immune Infiltration in Human Stanford Type A Aortic Dissection: Novel Insights from Bioinformatics Analyses.", "doi": "10.1155/2022/6184802", "pmid": "35480868", "authors": ["Fuqiang Liu", "Tao Wei", "Lin Liu", "Fangxia Hou", "Cuixiang Xu", "Hua Guo", "Wei Zhang", "Meijuan Ma", "Yulian Zhang", "Qi Yu", "Junkui Wang"], "journal": "Oxidative medicine and cellular longevity", "year": 2022, "abstract": "Background: Stanford type A aortic dissection (TAAD) is one of the most life-threatening cardiovascular emergencies with high mortality and morbidity, and necroptosis is a newly identified type of programmed cell death and contributes to the pathogenesis of various cardiovascular diseases. However, the role of necroptosis in TAAD has not been elucidated. This study was aimed at determining the role of necroptosis in TAAD using bioinformatics analyses.\nMethods: The RNA sequencing dataset GSE153434 and the microarray dataset GSE52093 were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes of necroptosis (NRDEGs) were identified based on differentially expressed genes (DEGs) and necroptosis gene set. Gene set enrichment analysis (GSEA) was applied to evaluate the gene enrichment signaling pathway in TAAD. The STRING database and Cytoscape software were used to establish and visualize protein-protein interaction (PPI) networks and identify the key functional modules of NRDEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of NRDEGs were also performed. Additionally, Spearman correlations were used to construct the necroptosis-related transcription factor-target genes regulatory network, immune infiltration patterns were analyzed using the ImmuCellAI algorithm, and the correlation between immune cell-type abundance and NRDEGs expression was investigated. The expression levels of NRDEGs and immune infiltration were additionally verified in the GSE52093 dataset.\nResults: We found that the necroptosis pathway was considerably enriched and activated in TAAD samples. Overall, 25 NRDEGs were identified including MLKL, RIPK1, and FADD, and among them, 18 were verified in the validation set. Moreover, GO and KEGG enrichment analyses found that NRDEGs were primarily involved in the tumor necrosis factor signaling pathway, nucleotide-binding oligomerization domain-like receptor signaling pathway, and interleukin-17 signaling pathway. The imbalance of Th17/Treg cells was identified in the TAAD samples. Furthermore, correlation analysis indicated that expression of NRDEGs was positively associated with proinflammatory immune-cell infiltrations and negatively associated with anti-inflammatory or regulatory immune-cell infiltrations.\nConclusions: The present findings suggest that necroptosis phenomenon exists in TAAD and correlates with immune cell infiltration, which indicate necroptosis may promote the development of TAAD through activating immune infiltration and immune response. This study paves a new road to future investigation of the pathogenic mechanisms and therapeutic strategies for TAAD.", "claims": [{"id": "claim-method", "statement": "Gene set enrichment analysis (GSEA) was applied to evaluate the gene enrichment signaling pathway in TAAD.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35480868", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Gene set enrichment analysis (GSEA) was applied to evaluate the gene enrichment signaling pathway in TAAD."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data are public and can be downloaded from the GEO database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35480868", "locator": "sections[21] \"Data Availability\" paragraph 2", "quote": "The data are public and can be downloaded from the GEO database."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The necroptosis pathway was considerably enriched and activated in TAAD samples.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35480868", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We found that the necroptosis pathway was considerably enriched and activated in TAAD samples."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The necroptosis pathway was considerably enriched and activated in TAAD samples.", "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:35480868"], "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:GSE153434"], "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:GSE153434"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35480868", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2022/6184802", "sha256": "sha256:c4a45bbe793e35f4363f2e9c061a8c99cb24df3fd8876e7f2724566377a2f387", "bytes": 27298, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2022/6184802", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9036163", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE153434", "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=GSE153434", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE153434", "version": null, "note": "The data are public and can be downloaded from the GEO database.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data are public and can be downloaded from the GEO database.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4644214", "GSM4644215", "GSM4644216", "GSM4644217", "GSM4644218", "GSM4644219", "GSM4644220", "GSM4644221", "GSM4644222", "GSM4644223", "GSM4644224", "GSM4644225", "GSM4644226", "GSM4644227", "GSM4644228", "GSM4644229", "GSM4644230", "GSM4644231", "GSM4644232", "GSM4644233"], "sample_count": 20, "group_sizes": null, "group_sizes_basis": null, "platform": "20795", "taxon": "Homo sapiens", "title": "Exaggerated autophagy as molecular characterization of Stanford type A aortic dissection: A transcriptome analysis of human ascending aortic tissues", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE52093", "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=GSE52093", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE52093", "version": null, "note": "The data are public and can be downloaded from the GEO database.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data are public and can be downloaded from the GEO database.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1259275", "GSM1259276", "GSM1259277", "GSM1259278", "GSM1259279", "GSM1259280", "GSM1259281", "GSM1259282", "GSM1259283", "GSM1259284", "GSM1259285", "GSM1259286"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "Genome-wide analysis of gene expression of ascending aorta from patients with acute Stanford type A aortic dissection", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE153434 not downloaded", "asset:data:geo:GSE153434 licence not read", "asset:data:geo:GSE52093 not downloaded", "asset:data:geo:GSE52093 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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-2", "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-3", "family": null, "specific": null, "label": "Gene set enrichment analysis (GSEA)", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Gene set enrichment analysis (GSEA) was applied to evaluate the gene enrichment signaling pathway in TAAD."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network."}, "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": ["GSE153434", "GSE52093"], "resolved_accessions": ["GSE153434", "GSE52093"], "statements": ["The data are public and can be downloaded from the GEO database."], "basis": "The paper names GSE153434, GSE52093 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "assets": ["source:pmid:35480868", "data:geo:GSE153434"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE153434"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:43:49Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 8077, "completion_tokens": 1155, "cached_tokens": 128}}, "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:35480868", "type": "paper", "label": "pmid:35480868"}, {"id": "source:pmid:35480868", "type": "manuscript", "label": "PMID 35480868 full text"}, {"id": "data:geo:GSE153434", "type": "dataset", "label": "GEO GSE153434"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35480868", "type": "paper", "label": "pmid:35480868"}, {"id": "source:pmid:35480868", "type": "manuscript", "label": "PMID 35480868 full text"}, {"id": "data:geo:GSE153434", "type": "dataset", "label": "GEO GSE153434"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35480868", "type": "extraction", "used": ["source:pmid:35480868"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE153434", "type": "accession_resolution", "used": ["data:geo:GSE153434"], "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:35480868", "parent_hash": "sha256:14e2539cd3d954aec9621ff53b80bc90c4b6989b36a934110e64baf40a8cdc2d", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE153434 licence not read", "asset:data:geo:GSE153434 not downloaded", "asset:data:geo:GSE52093 licence not read", "asset:data:geo:GSE52093 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["using bioinformatics analyses. Methods: The RNA sequencing dataset GSE153434 and the microarray dataset"], "order_basis": "paper_text_order:558", "id": "assay:1"}, {"role": "analysis", "definition_id": "network_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["protein-protein interaction"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}