Identification of CXC Chemokine Receptor 2 (CXCR2) as a Novel Eosinophils-Independent Diagnostic Biomarker of Pediatric Eosinophilic Esophagitis by Integrated Bioinformatic and Machine-Learning Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38328342", "kind": "science-record", "revision": 4, "content_hash": "sha256:0ca1dc20211e34b3754772fa5dd922e50face7e4588e3beb134a0b27511a6faf", "created_at": "2026-11-01T19:20:16Z", "updated_at": "2026-11-01T22:53:38Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of CXC Chemokine Receptor 2 (CXCR2) as a Novel Eosinophils-Independent Diagnostic Biomarker of Pediatric Eosinophilic Esophagitis by Integrated Bioinformatic and Machine-Learning Analysis.", "doi": "10.2147/ITT.S439289", "pmid": "38328342", "authors": ["Junhao Wu", "Caihan Duan", "Chaoqun Han", "Xiaohua Hou"], "journal": "ImmunoTargets and therapy", "year": 2024, "abstract": "Background: Eosinophilic esophagitis (EoE) is a complex allergic condition frequently accompanied by various atopic comorbidities in children, which significantly affects their life qualities. Therefore, this study aimed to evaluate pivotal molecular markers that may facilitate the diagnosis of EoE in pediatric patients.\nMethods: Three available EoE-associated gene expression datasets in children: GSE184182, GSE 197702, GSE55794, along with GSE173895 were downloaded from the GEO database. Differentially expressed genes (DEGs) identified by \"limma\" were intersected with key module genes identified by weighted gene co-expression network analysis (WGCNA), and the shared genes went through functional enrichment analysis. The protein-protein interaction (PPI) network and the machine learning algorithms: least absolute shrinkage and selection operator (LASSO), random forest (RF), and XGBoost were used to reveal candidate diagnostic markers for EoE. The receiver operating characteristic (ROC) curve showed the efficacy of differential diagnosis of this marker, along with online databases predicting its molecular regulatory network. Finally, we performed gene set enrichment analysis (GSEA) and assessed immune cell infiltration of EoE/control samples by using the CIBERSORT algorithm. The correlations between the key diagnostic biomarker and immune cells were also investigated.\nResults: The intersection of 936 DEGs and 1446 key module genes in EoE generated 567 genes, which were primarily enriched in immune regulation. Following the construction of the PPI network and filtration by machine learning, CXCR2 served as a potential diagnostic biomarker of pediatric EoE with a perfect diagnostic efficacy (AUC = ~1.00) in regional tissue/peripheral whole blood samples. Multiple infiltrated immune cells were observed to participate in disrupting the homeostasis of esophageal epithelium to varying degrees.\nConclusion: The immune-correlated CXCR2 gene was proved to be a promising diagnostic indicator for EoE, and dysregulated regulatory T cells (Tregs)/neutrophils might play a crucial role in the pathogenesis of EoE in children.", "claims": [{"id": "claim-method", "statement": "The “Limma” R package was utilized to identify DEGs between the pediatric EoE group and control group in the discovery dataset,30 based on |log2(Foldchange)| > 1 and adjusted P value < 0.05 (adopting Benjamini and Hochberg’s method to control the false discovery rate).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38328342", "locator": "sections[4] \"Identification of Differentially Expressed Genes (DEGs)\" paragraph 2", "quote": "The “Limma” R package was utilized to identify DEGs between the pediatric EoE group and control group in the discovery dataset,30 based on |log2(Foldchange)| > 1 and adjusted P value < 0.05 (adopting Benjamini and Hochberg’s method to control the false discovery rate)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets utilized in this study could be accessed from online repositories GEO, with accession number(s) GSE184182, GSE197702; GSE156651; GSE41687; GSE148381; GSE55794.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38328342", "locator": "sections[29] \"Data Sharing Statement\" paragraph 2", "quote": "The datasets utilized in this study could be accessed from online repositories GEO, with accession number(s) GSE184182, GSE197702; GSE156651; GSE41687; GSE148381; GSE55794."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Such algorithms collectively enriched the CXCR2 gene (Figure 5D), of which the area under the ROC curve (AUC) indicated its well diagnostic performance in both the discovery (AUC = 0.990) and the validation (AUC = 0.986) dataset.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38328342", "locator": "sections[19] \"Identification of Hub Pediatric EoE Diagnostic Biomarkers by Machine-Learning Algorithms\" paragraph 2", "quote": "Such algorithms collectively enriched the CXCR2 gene (Figure 5D), of which the area under the ROC curve (AUC) indicated its well diagnostic performance in both the discovery (AUC = 0.990) and the validation (AUC = 0.986) dataset."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Such algorithms collectively enriched the CXCR2 gene (Figure 5D), of which the area under the ROC curve (AUC) indicated its well diagnostic performance in both the discovery (AUC = 0.990) and the validation (AUC = 0.986) dataset.", "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:38328342"], "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:GSE148381"], "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:GSE148381"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38328342", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/ITT.S439289", "sha256": 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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": ["GSE184182", "GSE197702", "GSE156651", "GSE41687", "GSE148381", "GSE55794"], "resolved_accessions": ["GSE184182", "GSE197702", "GSE156651", "GSE41687", "GSE148381", "GSE55794"], "statements": ["The datasets utilized in this study could be accessed from online repositories GEO, with accession number(s) GSE184182, GSE197702; GSE156651; GSE41687; GSE148381; GSE55794."], "basis": "The paper names GSE184182, GSE197702, GSE156651, GSE41687, GSE148381, GSE55794 in Gene Expression Omnibus (GEO) Database 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:38328342", "data:geo:GSE148381"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE148381"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:07:58Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 19353, "completion_tokens": 2124, "cached_tokens": 256}}, "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:38328342", "type": "paper", "label": "pmid:38328342"}, {"id": "source:pmid:38328342", "type": "manuscript", "label": "PMID 38328342 full text"}, {"id": "data:geo:GSE148381", "type": "dataset", "label": "GEO GSE148381"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38328342", "type": "paper", "label": "pmid:38328342"}, {"id": "source:pmid:38328342", "type": "manuscript", "label": "PMID 38328342 full text"}, {"id": "data:geo:GSE148381", "type": "dataset", "label": "GEO GSE148381"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38328342", "type": "extraction", "used": ["source:pmid:38328342"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE148381", "type": "accession_resolution", "used": ["data:geo:GSE148381"], "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:38328342", "parent_hash": "sha256:785eb5cca66f5dc0408375fe7ae721577f59133ca7d78d3b208967ff97b65152", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE148381 licence not read", "asset:data:geo:GSE148381 not downloaded", "asset:data:geo:GSE156651 licence not read", "asset:data:geo:GSE156651 not downloaded", "asset:data:geo:GSE184182 licence not read", "asset:data:geo:GSE184182 not downloaded", "asset:data:geo:GSE197702 licence not read", "asset:data:geo:GSE197702 not downloaded", "asset:data:geo:GSE41687 licence not read", "asset:data:geo:GSE41687 not downloaded", "asset:data:geo:GSE55794 licence not read", "asset:data:geo:GSE55794 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["The “Limma” R package was utilized to identify DEGs between the pediatric EoE group and control group in the discovery dataset,30 based on |log2(Foldchange)| > 1 and adjusted P value < 0.05 (adopting Benjamini and Hochberg’s method to control the false discovery rate)."], "order_basis": "analysis_only", "id": "assay:1"}]}