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pmid:33994801
Identifying the Potential Therapeutic Targets for Atopic Dermatitis Through the Immune Infiltration Analysis and Construction of a ceRNA Network.
Shixiong Peng · Mengjiao Chen · Ming Yin · Hao Feng
Clinical, cosmetic and investigational dermatology · 2021 doi:10.2147/CCID.S310426
Paper
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Experiment
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Data
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Complete file
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We explored the hub genes by the enrichment analysis and the protein-protein interaction (PPI) analysis. Moreover, we estimated immune cell types and their proportions by ImmucellAI. GSE121212 dataset validation was performed to verify the robustness of the hub genes. Then, a ceRNA network was constructed by the miRWalk, miRNet, miRDB, DIANA, TargetScan, and starbase database. Finally, gene expression analysis was performed by using RT-qPCR.\nRESULTS: In total, we detected 22 differentially expressed genes (DEGs), which contained 8 downregulated genes and 14 upregulated genes. There were 5 hub genes confirmed as key genes through PPI network analysis and the ROC curves. KEGG pathway analysis revealed that they were significantly enriched in the IL-17 signaling pathway and GO analysis showed mainly in the immune cell chemotaxis. The immune infiltration profiles were different between normal controls and AD, and each of the key genes (S100A7, S100A8, S100A9, and LCE3D) was significantly correlated with the main infiltration cell of AD. A lncRNA-miRNA-mRNA ceRNA network containing the key genes was constructed, and NEAT1 and XIST, the core of ceRNA network, were significantly overexpressing verified by RT-qPCR in AD patients.\nCONCLUSION: Altogether, the key genes and their ceRNA network provided a novel perspective to the immunomodulation of AD, which may be potential and new therapeutic targets for AD.", "claims": [{"id": "claim-method", "statement": "Two groups’ data were analyzed through the unpaired Student’s t-test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33994801", "locator": "sections[11] \"Statistical Analysis\" paragraph 2", "quote": "Two groups’ data were analyzed through the unpaired Student’s t-test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The AD patients’ RNA expressed datasets (GSE63741, GSE124700) were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/). 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"structure": {"pmcid": "PMC8112859", "section_index": 15, "section_title": "PPI Network and Module Analyses", "row_count": 6, "column_count": 5}, "table": {"label": "Table 5", "caption": "The Top 5 Hub Genes", "rows": [["Genes", "Description", "Degree", "MCC", "Expression Change"], ["HBB", "Hemoglobin subunit beta", "4", "4", "Downregulated"], ["LCE3D", "Late cornified envelope 3D", "3", "3", "Upregulated"], ["S100A7", "S100 calcium binding protein A7", "4", "4", "Upregulated"], ["S100A9", "S100 calcium binding protein A9", "3", "4", "Upregulated"], ["S100A8", "S100 calcium binding protein A8", "3", "4", "Upregulated"]], "row_count": 6, "column_count": 5, "numeric_cells": 17, "header_rows": 1, "locator": "section[15]/table-wrap[1]#t0005"}}, {"id": "asset:table:pmid:33994801:6", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:f0f9eccf67d98975ad842eb97d8a91317517e40e2c3edaafda07d83144f6fa1c", "bytes": 476, "access": 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null, "sha256": "sha256:98cbc775f9c966ced0fd9d28042327e7e243c578759404a860b207ca4baa1b36", "bytes": 996, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[19]/table-wrap[1]#t0007", "version": null, "note": "The miRNAs Targeting Hub Genes", "structure": {"pmcid": "PMC8112859", "section_index": 19, "section_title": "The lncRNA-miRNA-mRNA ceRNA Network of AD", "row_count": 15, "column_count": 2}, "table": {"label": "Table 7", "caption": "The miRNAs Targeting Hub Genes", "rows": [["Genes", "The miRNAs"], ["HBB", "hsa-miR-6851-3p hsa-miR-3922-5p hsa-miR-361-3p hsa-miR-1910-3p"], ["hsa-miR-6511a-5p hsa-miR-3914 hsa-miR-33a-3p hsa-miR-5009-5p"], ["hsa-miR-6822-5p hsa-miR-4307 hsa-miR-4423-3p hsa-miR-6750-5p"], ["hsa-miR-6886-3p hsa-miR-8058"], ["LCE3D", "hsa-miR-193b-5p hsa-miR-1224-5p hsa-miR-3170 hsa-miR-4700-5p"], ["hsa-miR-4320 hsa-miR-6763-5p hsa-miR-4667-5p hsa-miR-3690"], ["hsa-miR-4471 hsa-miR-513a-5p hsa-miR-4269 hsa-miR-4314"], ["hsa-miR-6750-5p hsa-miR-6855-5p hsa-miR-4691-5p hsa-miR-6792-3p"], ["hsa-miR-5004-5p"], ["S100A7", "hsa-miR-30c-2-3p hsa-miR-1343-3p hsa-miR-6788-5p hsa-miR-6852-5p"], ["S100A8", "hsa-miR-98-5p"], ["S100A9", "hsa-miR-4701-5p hsa-miR-132-5p hsa-miR-588 hsa-miR-1204"], ["hsa-miR-3677-5p hsa-miR-940 hsa-miR-6878-3p"], ["hsa-miR-766-5p hsa-miR-92a-1-5p hsa-miR-660-3p"]], "row_count": 15, "column_count": 2, "numeric_cells": 17, "header_rows": 1, "locator": "section[19]/table-wrap[1]#t0007"}}, {"id": "asset:table:pmid:33994801:8", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7d7a84b1b4a29e650a8d0639771a79df8d759615dcec5e09bc2fa4b7fe2de4b5", "bytes": 515, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[19]/table-wrap[2]#t0008", "version": null, "note": "The ceRNA Network of AD", "structure": {"pmcid": "PMC8112859", "section_index": 19, "section_title": "The lncRNA-miRNA-mRNA ceRNA Network of AD", "row_count": 8, "column_count": 3}, "table": {"label": "Table 8", "caption": "The ceRNA Network of AD", "rows": [["mRNA", "miRNA", "lncRNA"], ["HBB", "hsa-miR-361-3p", "SNHG1, GUSBP11, MALAT1"], ["LCE3D", "hsa-miR-1224-5p", "NEAT1"], ["S100A8", "hsa-miR-98-5p", "NUTM2A-AS1, TRG-AS1, XIST, TTTY15"], ["S100A9", "hsa-miR-766-5p", "RMRP, STAG3L5P-PVRIG2P-PILRB, XIST"], ["NEAT1, LINC00894, KCNQ1OT1, NUTM2A-AS1"], ["hsa-miR-588", "XIST,NEAT1"], ["hsa-miR-132-5p", "TTN-AS1"]], "row_count": 8, "column_count": 3, "numeric_cells": 11, "header_rows": 1, "locator": "section[19]/table-wrap[2]#t0008"}}], "gaps": ["asset:data:geo:GSE121212 not downloaded", "asset:data:geo:GSE121212 licence not read", "asset:data:geo:GSE124700 not downloaded", "asset:data:geo:GSE124700 licence not read", "asset:data:geo:GSE63741 not downloaded", "asset:data:geo:GSE63741 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": null, "specific": null, "label": "unpaired Student’s t-test", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Two groups’ data were analyzed through the unpaired Student’s t-test."}}], "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", 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE63741", "GSE124700", "GSE121212"], "resolved_accessions": ["GSE63741", "GSE124700", "GSE121212"], "statements": ["The AD patients’ RNA expressed datasets (GSE63741, GSE124700) were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/). GSE63741 included an RNA expression profile of 150 samples, containing 30 control samples and 30 AD samples, while GSE124700 included RNA expression datasets for 2 control samples and 2 AD samples (6 subjects)."], "basis": "The paper names GSE63741, GSE124700, GSE121212 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:33994801", "data:geo:GSE121212", "asset:table:pmid:33994801:1", "asset:table:pmid:33994801:2", "asset:table:pmid:33994801:3", "asset:table:pmid:33994801:4", "asset:table:pmid:33994801:5", "asset:table:pmid:33994801:6", "asset:table:pmid:33994801:7", "asset:table:pmid:33994801:8"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE121212"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:30:03Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 32894, "completion_tokens": 891, "cached_tokens": 785}}, "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:33994801", "type": "paper", "label": "pmid:33994801"}, {"id": "source:pmid:33994801", "type": "manuscript", "label": "PMID 33994801 full text"}, {"id": "data:geo:GSE121212", "type": "dataset", "label": "GEO GSE121212"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33994801", "type": "paper", "label": "pmid:33994801"}, {"id": "source:pmid:33994801", "type": "manuscript", "label": "PMID 33994801 full text"}, {"id": "data:geo:GSE121212", "type": "dataset", "label": "GEO GSE121212"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33994801", "type": "extraction", "used": ["source:pmid:33994801"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE121212", "type": "accession_resolution", "used": ["data:geo:GSE121212"], "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:33994801", "parent_hash": "sha256:dba05a6f8f79aaa2d83aefc86993f8448aa38f1b7a923de999e0dd122ff9042c", "fork_of": null, "generation": 5}, "gaps": ["asset:data:geo:GSE121212 licence not read", "asset:data:geo:GSE121212 not downloaded", "asset:data:geo:GSE124700 licence not read", "asset:data:geo:GSE124700 not downloaded", "asset:data:geo:GSE63741 licence not read", "asset:data:geo:GSE63741 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["e expression analysis was performed by using RT-qPCR. RESULTS: In total, we detected 22 different", "ere significantly overexpressing verified by RT-qPCR in AD patients. CONCLUSION: Altogether, the", "xpression analysis was performed by using RT-qPCR. RESULTS: In total, we detected 22 different", "significantly overexpressing verified by RT-qPCR in AD patients. CONCLUSION: Altogether, the"], "order_basis": "paper_text_order:918", "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"}]}