M2 Macrophage Co-Expression Factors Correlate With Immune Phenotype and Predict Prognosis of Bladder Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33828973", "kind": "science-record", "revision": 6, "content_hash": "sha256:0987b0a5b8490db29e45334434765109ad5fb5b3d9e3d0c926a7fbecae71d081", "created_at": "2026-11-01T15:41:31Z", "updated_at": "2026-11-01T21:25:06Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "M2 Macrophage Co-Expression Factors Correlate With Immune Phenotype and Predict Prognosis of Bladder Cancer.", "doi": "10.3389/fonc.2021.609334", "pmid": "33828973", "authors": ["Yutao Wang", "Kexin Yan", "Jianfeng Wang", "Jiaxing Lin", "Jianbin Bi"], "journal": "Frontiers in oncology", "year": 2021, "abstract": "PURPOSE: Therapeutic targets of tumor-associated macrophages have been discovered and used clinically as immunotherapy. M2 macrophages are tumor-associated macrophages that promote cancer progression. This article explores the related factors and the effects of type M2 macrophages.\nMETHOD: We obtained bladder cancer (BC) sequencing data from TCGA and GSE31189. We used the CIBERSORT algorithm calculate M2 macrophage proportions among 22 type immune cells. The Estimate package was used to measure BC purity. M2 macrophage-related genes were selected using WGCNA. Receiver operating characteristic curves and Kaplan-Meier analyses were performed to determine the risk score, conducted for M2 macrophage-related factors. The Pearson test was used to determine the correlation among M2 macrophage-related genes, clinical phenotype, immune phenotype and tumor mutation burden (TMB). The TIMER database was used to calculate correlations among M2 macrophages and other cancers.\nRESULTS: Expression of four M2 macrophages co-expressed genes (CD163, CD209, CSF1, MMD) positively correlated with infiltration of M2 macrophages, which were enriched in the negative regulation of immune system process and the positive regulation of tumor necrosis factor production. M2 macrophage-related factors are robust biomarkers for predicting the BC and immune phenotypes. The Cox regression model built on these four co-expression factors showed a close correlation with outcome (AUC = 0.64). The four co-expression factors negatively correlated outcome and TMB.\nCONCLUSION: Four co-expressed genes promote high levels of infiltration of type M2 macrophages in the negative regulation of immune system processes and the positive regulation of tumor necrosis factor production processes. These co-expressed genes and the biological process they involve might suggest new strategies for regulation of chemotaxis in M2 macrophages.", "claims": [{"id": "claim-method", "statement": "Then, we generated a multi-Cox regression risk score model based on these genes: Risk score = 1 * CD163 + 1.007 * CD209 + 1.028 * CSF1 + 1.012 * MMD.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33828973", "locator": "sections[13] \"Survival and Prognostic Analysis\" paragraph 2", "quote": "Then, we generated a multi-Cox regression risk score model based on these genes: Risk score = 1 * CD163 + 1.007 * CD209 + 1.028 * CSF1 + 1.012 * MMD."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. These data can be found here: The TCGA-BLCA dataset used in this study could be obtained from TCGA database (https://cancergenome.nih.gov/). GEO datasets (GSE31189) used in this study could be obtained from GEO database (https://www.ncbi.nlm.nih.gov/geo/). genomic, transcriptomic, and clinical information from patients with metastatic urothelial cancer treated with an anti-PD-L1 agent (atezolizumab) is obtained under the Creative Commons 3.0 license and can be downloaded from http://research-pub.gene.com/IMvigor210CoreBiologies.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33828973", "locator": "sections[19] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. These data can be found here: The TCGA-BLCA dataset used in this study could be obtained from TCGA database (https://cancergenome.nih.gov/). GEO datasets (GSE31189) used in this study could be obtained from GEO database (https://www.ncbi.nlm.nih.gov/geo/). genomic, transcriptomic, and clinical information from patients with metastatic urothelial cancer treated with an anti-PD-L1 agent (atezolizumab) is obtained under the Creative Commons 3.0 license and can be downloaded from http://research-pub.gene.com/IMvigor210CoreBiologies."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:33828973"], "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:GSE31189"], "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:GSE31189"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33828973", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fonc.2021.609334", "sha256": "sha256:bd7919339a05dba59dc5a153d8a9fadf2a233fb725dc440911a563f937f592a2", "bytes": 32782, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fonc.2021.609334", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8019942", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE31189", "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=GSE31189", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE31189", "version": null, "note": "Publicly available datasets were analyzed in this study. These data can be found here: The TCGA-BLCA dataset used in this study could be obtained from TCGA database (https://cancergenome.nih.gov/). GEO datasets (GSE31189) used in this study could be obtained from GEO database (https://www.ncbi.nlm.nih.gov/geo/). genomic, transcriptomic, and clinical information from patients with metastatic urothelial cancer treated with an anti-PD-L1 agent (atezolizumab) is obtained under the Creative Commons 3.0 license and can be downloaded from http://research-pub.gene.com/IMvigor210CoreBiologies.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. These data can be found here: The TCGA-BLCA dataset used in this study could be obtained from TCGA database (https://cancergenome.nih.gov/). GEO datasets (GSE31189) used in this study could be obtained from GEO database (https://www.ncbi.nlm.nih.gov/geo/). genomic, transcriptomic, and clinical information from patients with metastatic urothelial cancer treated with an anti-PD-L1 agent (atezolizumab) is obtained under the Creative Commons 3.0 license and can be downloaded from http://research-pub.gene.com/IMvigor210CoreBiologies.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM773124", "GSM773125", "GSM773126", "GSM773127", "GSM773128", "GSM773129", "GSM773130", "GSM773131", "GSM773132", "GSM773133", "GSM773134", "GSM773135", "GSM773136", "GSM773137", "GSM773138", "GSM773139", "GSM773140", "GSM773141", "GSM773142", "GSM773143", "GSM773144", "GSM773145", "GSM773146", "GSM773147", "GSM773148", "GSM773149", "GSM773150", "GSM773151", "GSM773152", "GSM773153", "GSM773154", "GSM773155", "GSM773156", "GSM773157", "GSM773158", "GSM773159", "GSM773160", "GSM773161", "GSM773162", "GSM773163", "GSM773164", "GSM773165", "GSM773166", "GSM773167", "GSM773168", "GSM773169", "GSM773170", "GSM773171", "GSM773172", "GSM773173", "GSM773174", "GSM773175", "GSM773176", "GSM773177", "GSM773178", "GSM773179", "GSM773180", "GSM773181", "GSM773182", "GSM773183", "GSM773184", "GSM773185", "GSM773186", "GSM773187", "GSM773188", "GSM773189", "GSM773190", "GSM773191", "GSM773192", "GSM773193", "GSM773194", "GSM773195", "GSM773196", "GSM773197", "GSM773198", "GSM773199", "GSM773200", "GSM773201", "GSM773202", "GSM773203", "GSM773204", "GSM773205", "GSM773206", "GSM773207", "GSM773208", "GSM773209", "GSM773210", "GSM773211", "GSM773212", "GSM773213", "GSM773214", "GSM773215"], "sample_count": 92, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Molecular Biomarker Signature for Bladder Cancer Detection", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33828973:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:770253092be80002591733e875d6342f310f436de7c8825aa31773598359d774", "bytes": 787, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#T2", "version": null, "note": "The correlation of intersecting genes with M2 macrophages in GSE31189.", "structure": {"pmcid": "PMC8019942", "section_index": 5, "section_title": "Intersection Function Analysis", "row_count": 21, "column_count": 3}, "table": {"label": "Table 2", "caption": "The correlation of intersecting genes with M2 macrophages in GSE31189.", "rows": [["ID", "GS.Macrophage.M2", "P - 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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": ["GSE31189"], "resolved_accessions": ["GSE31189"], "statements": ["Publicly available datasets were analyzed in this study. These data can be found here: The TCGA-BLCA dataset used in this study could be obtained from TCGA database (https://cancergenome.nih.gov/). GEO datasets (GSE31189) used in this study could be obtained from GEO database (https://www.ncbi.nlm.nih.gov/geo/). genomic, transcriptomic, and clinical information from patients with metastatic urothelial cancer treated with an anti-PD-L1 agent (atezolizumab) is obtained under the Creative Commons 3.0 license and can be downloaded from http://research-pub.gene.com/IMvigor210CoreBiologies."], "basis": "The paper names GSE31189 in GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:33828973", "data:geo:GSE31189", "asset:table:pmid:33828973:1", "asset:table:pmid:33828973:2", "asset:table:pmid:33828973:3", "asset:table:pmid:33828973:4", "asset:table:pmid:33828973:5"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE31189"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:28:55Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 26269, "completion_tokens": 2345, "cached_tokens": 784}}, "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:33828973", "type": "paper", "label": "pmid:33828973"}, {"id": "source:pmid:33828973", "type": "manuscript", "label": "PMID 33828973 full text"}, {"id": "data:geo:GSE31189", "type": "dataset", "label": "GEO GSE31189"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33828973", "type": "paper", "label": "pmid:33828973"}, {"id": "source:pmid:33828973", "type": "manuscript", "label": "PMID 33828973 full text"}, {"id": "data:geo:GSE31189", "type": "dataset", "label": "GEO GSE31189"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33828973", "type": "extraction", "used": ["source:pmid:33828973"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE31189", "type": "accession_resolution", "used": ["data:geo:GSE31189"], "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:33828973", "parent_hash": "sha256:bd2d504d28351ea4db46cf25541706ed890ea83f166013ef686812c3c83413cf", "fork_of": null, "generation": 5}, "gaps": ["asset:data:geo:GSE31189 licence not read", "asset:data:geo:GSE31189 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Then, we generated a multi-Cox regression risk score model based on these genes: Risk score = 1 * CD163 + 1.007 * CD209 + 1.028 * CSF1 + 1.012 * MMD."], "order_basis": "analysis_only", "id": "assay:1"}]}