Bioinformatics analysis identifies WNK1 gene as a potential biomarker for cholangiocarcinoma diagnosis and immune infiltration.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39674642", "kind": "science-record", "revision": 3, "content_hash": "sha256:42f87c0695b8a936d34c401b28925b189551b3f4cda1c812920ee61867ddfced", "created_at": "2026-11-01T20:29:58Z", "updated_at": "2026-11-01T22:13:19Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatics analysis identifies WNK1 gene as a potential biomarker for cholangiocarcinoma diagnosis and immune infiltration.", "doi": "10.1016/j.jgeb.2024.100426", "pmid": "39674642", "authors": ["Qi Sun", "Xianli Lei", "Xiangrong Meng", "Caijun Zha", "Lei Yan", "Wenjing Zhang"], "journal": "Journal, genetic engineering & biotechnology", "year": 2024, "abstract": "BACKGROUND: Cholangiocarcinoma (CHOL) is a malignant epithelial carcinoma of the digestive system with poor prognosis and high mortality. WNK lysine deficient protein kinase 1 (WNK1) is known to be associated with tumorigenesis in various cancers. However, the relationship between WNK1 and CHOL development, as well as the potential mechanisms involved, remains poorly understood.\nMETHODS: Microarray datasets of CHOL (GSE22633 and GSE32879) were retrieved from the Gene Expression Omnibus (GEO) database. Functional enrichment and immunoinfiltration analyses were performed for genes co-expressed with WNK1. GraphPad Prism 9 was utilized for statistical data analysis and the construction of receiver operating characteristic (ROC) curves. The impact of WNK1 on the CHOL tumor microenvironment was analyzed using Tumor Immune Estimation Resource (TIMER), Venn diagrams, STRING, and TISIDB database for information on WNK1-related chemokines and chemokine receptors. Protein-protein interaction (PPI) networks were used to predict transcription factors and microRNAs interacting with WNK1 and the associated hub genes.\nRESULTS: Differential expression of WNK1 was observed between CHOL and normal samples, suggesting its diagnostic value. Functional analysis showed that WNK1 and its associated genes were primarily enriched in pathways such as leukocyte transendothelial migration and chemokine signaling. Neutrophils were the only type of infiltrating immune cells associated with WNK1 in the CHOL tumor microenvironment (TME). VEGFA and ALB were identified as hub genes, and X-C motif chemokine receptor 1 (XCR1) and C-X-C motif chemokine ligand 5 (CXCL5) were identified as core chemokines and chemokine receptors related to WNK1 and neutrophil infiltration in CHOL.\nCONCLUSIONS: Based on network analysis and the summary of previous studies, it was proposed that CHOL tumor cells secrete CXCL5, leading to neutrophil recruitment to the tumor microenvironment. Vascular endothelial growth factor A (VEGFA) released by the infiltrating neutrophils is suggested to promote overexpression of WNK1 by tumor cells, activating the VEGFA downstream pathway to promote angiogenesis and tumor progression.", "claims": [{"id": "claim-method", "statement": "Receiver operating characteristic (ROC) curves were drawn using data from the GSE32879 dataset and was visualized using GraphPad Prism 9.0.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39674642", "locator": "sections[13] \"Statistical analysis\" paragraph 2", "quote": "Receiver operating characteristic (ROC) curves were drawn using data from the GSE32879 dataset and was visualized using GraphPad Prism 9.0."}], "state": "complete"}, {"id": "claim-data-access", "statement": "In this study, two public datasets were used, GSE32879 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32879) and GSE22633 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22633).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39674642", "locator": "sections[22] \"Conclusions\" paragraph 6", "quote": "In this study, two public datasets were used, GSE32879 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32879) and GSE22633 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22633)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "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:39674642"], "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:GSE22633"], "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:GSE22633"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39674642", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.jgeb.2024.100426", "sha256": "sha256:5d15a071c2b82d7639e2e28b74aec596a212db8b5124039f24b4aba8b8ca509d", "bytes": 28351, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.jgeb.2024.100426", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11465147", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE22633", "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=GSE22633", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE22633", "version": null, "note": "In this study, two public datasets were used, GSE32879 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32879) and GSE22633 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22633).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "In this study, two public datasets were used, GSE32879 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32879) and GSE22633 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22633).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM561095", "GSM561096", "GSM561097", "GSM561098", "GSM561099", "GSM561100", "GSM561101", "GSM561102", "GSM561103", "GSM561104", "GSM561105", "GSM561106", "GSM561107", "GSM561108", "GSM561109", "GSM561110", "GSM561111", "GSM561112", "GSM561113", "GSM561114", "GSM561115", "GSM561116", "GSM561117", "GSM561118", "GSM561119", "GSM561120", "GSM561121", "GSM561122", "GSM561123", "GSM561124", "GSM561125", "GSM561126", "GSM561127", "GSM561128", "GSM561129", "GSM561130", "GSM561131", "GSM561132", "GSM561133", "GSM561134", "GSM561135", "GSM561136", "GSM561137", "GSM561138", "GSM561139", "GSM561140", "GSM561141", "GSM561142", "GSM561143", "GSM561144", "GSM561145", "GSM561146", "GSM561147", "GSM561148", "GSM561149", "GSM561150", "GSM561151", "GSM561152", "GSM561153", "GSM561154", "GSM561155", "GSM561156", "GSM561157"], "sample_count": 63, "group_sizes": null, "group_sizes_basis": null, "platform": "6102", "taxon": "Homo sapiens", "title": "Genome-Wide Molecular Signature of Cholangiocarcinoma and Its Trandifferentation-Related Genes", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE32879", "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=GSE32879", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE32879", "version": null, "note": "In this study, two public datasets were used, GSE32879 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32879) and GSE22633 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22633).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "In this study, two public datasets were used, GSE32879 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32879) and GSE22633 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22633).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM813712", "GSM813713", "GSM813714", "GSM813715", "GSM813716", "GSM813717", "GSM813718", "GSM813719", "GSM813720", "GSM813721", "GSM813722", "GSM813723", "GSM813724", "GSM813725", "GSM813726", "GSM813727", "GSM813728", "GSM813729", "GSM813730", "GSM813731", "GSM813732", "GSM813733", "GSM813734", "GSM813735", "GSM813736", "GSM813737", "GSM813738", "GSM813739", "GSM813740", "GSM813741", "GSM813742", "GSM813743", "GSM813744", "GSM813745", "GSM813746", "GSM813747", "GSM813748"], "sample_count": 37, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Integrative Transcriptomic Profiling reveals Hepatic Stem-like Phenotype and Interplay of EMT and miR-200c in Intrahepatic Cholangiocarcinoma [mRNA]", "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:GSE22633 not downloaded", "asset:data:geo:GSE22633 licence not read", "asset:data:geo:GSE32879 not downloaded", "asset:data:geo:GSE32879 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": "centrality", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "Centrality"}}, {"id": "method-3", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.8, "band": "high", "quote": "ROC curve"}}, {"id": "method-4", "family": null, "specific": null, "label": "receiver operating characteristic (ROC) curve analysis", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Receiver operating characteristic (ROC) curves were drawn using data from the GSE32879 dataset and was visualized using GraphPad Prism 9.0."}}], "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": ["GSE32879", "GSE22633"], "resolved_accessions": ["GSE32879", "GSE22633"], "statements": ["In this study, two public datasets were used, GSE32879 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32879) and GSE22633 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22633)."], "basis": "The paper names GSE32879, GSE22633 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:39674642", "data:geo:GSE22633"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE22633"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:41:46Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 8969, "completion_tokens": 1870, "cached_tokens": 264}}, "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:39674642", "type": "paper", "label": "pmid:39674642"}, {"id": "source:pmid:39674642", "type": "manuscript", "label": "PMID 39674642 full text"}, {"id": "data:geo:GSE22633", "type": "dataset", "label": "GEO GSE22633"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:39674642", "type": "paper", "label": "pmid:39674642"}, {"id": "source:pmid:39674642", "type": "manuscript", "label": "PMID 39674642 full text"}, {"id": "data:geo:GSE22633", "type": "dataset", "label": "GEO GSE22633"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-39674642", "type": "extraction", "used": ["source:pmid:39674642"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE22633", "type": "accession_resolution", "used": ["data:geo:GSE22633"], "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:39674642", "parent_hash": "sha256:a9ec283c5da618eaa0f38cc99e51af0fc605115e903cff6a0862d74c5b2860a6", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE22633 licence not read", "asset:data:geo:GSE22633 not downloaded", "asset:data:geo:GSE32879 licence not read", "asset:data:geo:GSE32879 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["nvolved, remains poorly understood. METHODS: Microarray datasets of CHOL (GSE22633 and GSE32879) wer"], "order_basis": "paper_text_order:474", "id": "assay:1"}, {"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": ["active and customizable functions to analyze RNA sequencing data based on the Genotype-Tissue Expression"], "order_basis": "paper_text_order:2680", "id": "assay:2"}, {"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:3"}]}