Identification of key genes involved in the recurrence of glioblastoma multiforme using weighted gene co-expression network analysis and differential expression analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34238116", "kind": "science-record", "revision": 6, "content_hash": "sha256:9212ab30fd7fb17f0e26250a9971ce98566477b68137aca090ddcc2cfdee32bc", "created_at": "2026-11-01T15:41:42Z", "updated_at": "2026-11-01T21:25:42Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of key genes involved in the recurrence of glioblastoma multiforme using weighted gene co-expression network analysis and differential expression analysis.", "doi": "10.1080/21655979.2021.1943986", "pmid": "34238116", "authors": ["Peng Ren", "JingYa Wang", "Lei Li", "XiaoWan Lin", "GuangHan Wu", "JiaYi Chen", "ZhiRui Zeng", "HongMei Zhang"], "journal": "Bioengineered", "year": 2021, "abstract": "Glioblastoma multiforme (GBM) is the most fatal malignancy, and despite extensive treatment, tumors inevitably recur. This study aimed to identify recurrence-associated molecules in GBM. The gene expression profile GSE139533, containing 70 primary and 47 recurrent GBM tissues and their corresponding clinical traits, was downloaded from the Gene Expression Omnibus (GEO) database and used for weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis. After identifying the hub genes which differentially expressed in recurrent GBM tissues and in the gene modules correlated with recurrence, data from the Chinese Glioma Genome Atlas (CCGA) and The Cancer Genome Atlas (TCGA) databases were analyzed with GSE43378 to determine the relationship between hub genes and patient prognosis. The diagnostic value of the identified hub genes was verified using 52 GBM tissues. Three gene modules were correlated with recurrence and 2623 genes were clustered in these clinically significant modules. Among these, 13 genes - EHF, TRPM1, FXYD4, CDH15, LHX5, TP73, FBN3, TLX1, C1QL4, COL2A, SEC61G, NEUROD4 and GPR139 - were differentially expressed in recurrent GBM samples; low LHX5 and TLX1 expression predicted poor outcomes. LHX5 and TLX1 expression showed weak positive relationships with Karnofsky performance scale scores. Additionally, LHX5 and TLX1 expression was found to be decreased in our recurrent GBM samples compared with that in primary samples; these genes exhibited high diagnostic value in distinguishing recurrent samples from primary samples. Our findings indicate that LHX5 and TLX1 might be involved in GBM recurrence and act as potential biomarkers for this condition.", "claims": [{"id": "claim-method", "statement": "Two gene expression profiles containing KPS scores for GBM patients were downloaded from The Cancer Genome Atlas (TCGA) (https://xenabrowser.net/datapages/) [28] and GEO (https://www.ncbi.nlm.nih.gov/gds; Accession: GSE43378) databases [29]. After normalization, the two gene profiles were merged using sva package v.3.12 (https://www.bioconductor.org/) [30]. Thereafter, the expression levels of LHX5 and TLX1 and the corresponding KPS scores for GBM patients were extracted. Finally, Pearson’s correlation analysis was performed to determine the relationship between the expression levels of LHX5 and TLX1 and the KPS scores in GBM patients.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34238116", "locator": "sections[9] \"Analysis of the relationship between the expression levels of hub genes and the Karnofsky performance scale (KPS) scores in GBM patients\" paragraph 2", "quote": "Two gene expression profiles containing KPS scores for GBM patients were downloaded from The Cancer Genome Atlas (TCGA) (https://xenabrowser.net/datapages/) [28] and GEO (https://www.ncbi.nlm.nih.gov/gds; Accession: GSE43378) databases [29]. After normalization, the two gene profiles were merged using sva package v.3.12 (https://www.bioconductor.org/) [30]. Thereafter, the expression levels of LHX5 and TLX1 and the corresponding KPS scores for GBM patients were extracted. Finally, Pearson’s correlation analysis was performed to determine the relationship between the expression levels of LHX5 and TLX1 and the KPS scores in GBM patients."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.\nGEO database (https://www.ncbi.nlm.nih.gov/gds)\nGSEA (https://software.broad institute. org/gsea/index.jsp)\nCCGA (http://www.cgga.org.cn/)\nTCGA (https://xenabrowser.net/datapages/)", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34238116", "locator": "sections[28] \"Data availability statement\" paragraphs 1-6", "quote": "The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.\nGEO database (https://www.ncbi.nlm.nih.gov/gds)\nGSEA (https://software.broad institute. org/gsea/index.jsp)\nCCGA (http://www.cgga.org.cn/)\nTCGA (https://xenabrowser.net/datapages/)"}], "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:34238116"], "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:GSE139533"], "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:GSE139533"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34238116", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1080/21655979.2021.1943986", "sha256": "sha256:e8704914bf4d939f4766661b155d132bce9283e877106cffe014cb7fcf284543", "bytes": 32458, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1080/21655979.2021.1943986", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8806787", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE139533", "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=GSE139533", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE139533", "version": null, "note": "The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.\nGEO database (https://www.ncbi.nlm.nih.gov/gds)\nGSEA (https://software.broad institute. org/gsea/index.jsp)\nCCGA (http://www.cgga.org.cn/)\nTCGA (https://xenabrowser.net/datapages/)", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.\nGEO database (https://www.ncbi.nlm.nih.gov/gds)\nGSEA (https://software.broad institute. org/gsea/index.jsp)\nCCGA (http://www.cgga.org.cn/)\nTCGA (https://xenabrowser.net/datapages/)", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4143105", "GSM4143106", "GSM4143107", "GSM4143108", "GSM4143109", "GSM4143110", "GSM4143111", "GSM4143112", "GSM4143113", "GSM4143114", "GSM4143115", "GSM4143116", "GSM4143117", "GSM4143118", "GSM4143119", "GSM4143120", "GSM4143121", "GSM4143122", "GSM4143123", "GSM4143124", "GSM4143125", "GSM4143126", "GSM4143127", "GSM4143128", "GSM4143129", "GSM4143130", "GSM4143131", "GSM4143132", "GSM4143133", "GSM4143134", "GSM4143135", "GSM4143136", "GSM4143137", "GSM4143138", "GSM4143139", "GSM4143140", "GSM4143141", "GSM4143142", "GSM4143143", "GSM4143144", "GSM4143145", "GSM4143146", "GSM4143147", "GSM4143148", "GSM4143149", "GSM4143150", "GSM4143151", "GSM4143152", "GSM4143153", "GSM4143154", "GSM4143155", "GSM4143156", "GSM4143157", "GSM4143158", "GSM4143159", "GSM4143160", "GSM4143161", "GSM4143162", "GSM4143163", "GSM4143164", "GSM4143165", "GSM4143166", "GSM4143167", "GSM4143168", "GSM4143169", "GSM4143170", "GSM4143171", "GSM4143172", "GSM4143173", "GSM4143174", "GSM4143175", "GSM4143176", "GSM4143177", "GSM4143178", "GSM4143179", "GSM4143180", "GSM4143181", "GSM4143182", "GSM4143183", "GSM4143184", "GSM4143185", "GSM4143186", "GSM4143187", "GSM4143188", "GSM4143189", "GSM4143190", "GSM4143191", "GSM4143192", "GSM4143193", "GSM4143194", "GSM4143195", "GSM4143196", "GSM4143197", "GSM4143198", "GSM4143199", "GSM4143200", "GSM4143201", "GSM4143202", "GSM4143203", "GSM4143204", "GSM4143205", "GSM4143206", "GSM4143207", "GSM4143208", "GSM4143209", "GSM4143210", "GSM4143211", "GSM4143212", "GSM4143213", "GSM4143214", "GSM4143215", "GSM4143216", "GSM4143217", "GSM4143218", "GSM4143219", "GSM4143220", "GSM4143221", "GSM4143222", "GSM4143223", "GSM4143224", "GSM4143225", "GSM4143226", "GSM4143227", "GSM4143228", "GSM4143229", "GSM4143230", "GSM4143231", "GSM4143232", "GSM4143233", "GSM4143234", "GSM4143235", "GSM4143236", "GSM4143237", "GSM4143238", "GSM4143239", "GSM4143240", "GSM4143241", "GSM4143242", "GSM4143243", "GSM4143244", "GSM4143245", "GSM4143246", "GSM4143247", "GSM4143248", "GSM4143249", "GSM4143250", "GSM4143251", "GSM4143252", "GSM4143253", "GSM4143254", "GSM4143255", "GSM4143256", "GSM4143257", "GSM4143258", "GSM4143259"], "sample_count": 155, "group_sizes": null, "group_sizes_basis": null, "platform": "18573", "taxon": "Homo sapiens", "title": "Intratumoral heterogeneity and longitudinal changes in gene expression predict differential drug sensitivity in newly diagnosed and recurrent glioblastoma", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE43378", "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=GSE43378", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE43378", "version": null, "note": "The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.\nGEO database (https://www.ncbi.nlm.nih.gov/gds)\nGSEA (https://software.broad institute. org/gsea/index.jsp)\nCCGA (http://www.cgga.org.cn/)\nTCGA (https://xenabrowser.net/datapages/)", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.\nGEO database (https://www.ncbi.nlm.nih.gov/gds)\nGSEA (https://software.broad institute. org/gsea/index.jsp)\nCCGA (http://www.cgga.org.cn/)\nTCGA (https://xenabrowser.net/datapages/)", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1061661", "GSM1061662", "GSM1061663", "GSM1061664", "GSM1061665", "GSM1061666", "GSM1061667", "GSM1061668", "GSM1061669", "GSM1061670", "GSM1061671", "GSM1061672", "GSM1061673", "GSM1061674", "GSM1061675", "GSM1061676", "GSM1061677", "GSM1061678", "GSM1061679", "GSM1061680", "GSM1061681", "GSM1061682", "GSM1061683", "GSM1061684", "GSM1061685", "GSM1061686", "GSM1061687", "GSM1061688", "GSM1061689", "GSM1061690", "GSM1061691", "GSM1061692", "GSM1061693", "GSM1061694", "GSM1061695", "GSM1061696", "GSM1061697", "GSM1061698", "GSM1061699", "GSM1061700", "GSM1061701", "GSM1061702", "GSM1061703", "GSM1061704", "GSM1061705", "GSM1061706", "GSM1061707", "GSM1061708", "GSM1061709", "GSM1061710"], "sample_count": 50, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Expression data from glioma patients", "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:34238116:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:c42bed8d4087f7f8776fa34ca76152fb6e2be8f9cf41d22282cf28c4ec3f1aa6", "bytes": 583, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[20]/table-wrap[1]#t0001", "version": null, "note": "Detail scores of T cell leukemia homeobox 1 (TLX1) and LIM homeobox 5 (LHX5) expression in the primary and recurrent glioblastoma multiforme (GBM) tissues", "structure": {"pmcid": "PMC8806787", "section_index": 20, "section_title": "LHX5 and TLX1 expression was decreased in the recurrent GBM tissues and exhibited high diagnostic value", "row_count": 6, "column_count": 9}, "table": {"label": "Table 1.", "caption": "Detail scores of T cell leukemia homeobox 1 (TLX1) and LIM homeobox 5 (LHX5) expression in the primary and recurrent glioblastoma multiforme (GBM) tissues", "rows": [["Genes", "Tissues", "Expression score"], ["0", "1", "2", "3", "4", "5", "6"], ["TLX1", "Primary tumor", "2", "3", "19", "10", "1", "0", "1"], ["Recurrence tumor", "6", "8", "1", "1", "0", "0", "0"], ["LHX5", "Primary tumor", "1", "1", "6", "14", "10", "2", "2"], ["Recurrence tumor", "6", "6", "1", "1", "2", "0", "0"]], "row_count": 6, "column_count": 9, "numeric_cells": 35, "header_rows": 2, "locator": "section[20]/table-wrap[1]#t0001"}}], "gaps": ["asset:data:geo:GSE139533 not downloaded", "asset:data:geo:GSE139533 licence not read", "asset:data:geo:GSE43378 not downloaded", "asset:data:geo:GSE43378 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "contingency_analysis", "specific": "chi_square", "label": "Categorical (contingency table) analysis", "dsl_operations": ["chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.8, "band": "high", "quote": "chi-square"}}, {"id": "method-2", "family": null, "specific": null, "label": "Pearson’s correlation analysis", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Two gene expression profiles containing KPS scores for GBM patients were downloaded from The Cancer Genome Atlas (TCGA) (https://xenabrowser.net/datapages/) [28] and GEO (https://www.ncbi.nlm.nih.gov/gds; Accession: GSE43378) databases [29]. After normalization, the two gene profiles were merged using sva package v.3.12 (https://www.bioconductor.org/) [30]. Thereafter, the expression levels of LHX5 and TLX1 and the corresponding KPS scores for GBM patients were extracted. Finally, Pearson’s correlation analysis was performed to determine the relationship between the expression levels of LHX5 and TLX1 and the KPS scores in GBM patients."}}], "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": ["chi_square_test"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: chi_square."}, "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": ["GSE139533", "GSE43378"], "resolved_accessions": ["GSE139533", "GSE43378"], "statements": ["The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.\nGEO database (https://www.ncbi.nlm.nih.gov/gds)\nGSEA (https://software.broad institute. org/gsea/index.jsp)\nCCGA (http://www.cgga.org.cn/)\nTCGA (https://xenabrowser.net/datapages/)"], "basis": "The paper names GSE139533, GSE43378 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": ["chi_square_test"], "assets": ["source:pmid:34238116", "data:geo:GSE139533", "asset:table:pmid:34238116:1"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE139533"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:32:11Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 24360, "completion_tokens": 1981, "cached_tokens": 8448}}, "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:34238116", "type": "paper", "label": "pmid:34238116"}, {"id": "source:pmid:34238116", "type": "manuscript", "label": "PMID 34238116 full text"}, {"id": "data:geo:GSE139533", "type": "dataset", "label": "GEO GSE139533"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34238116", "type": "paper", "label": "pmid:34238116"}, {"id": "source:pmid:34238116", "type": "manuscript", "label": "PMID 34238116 full text"}, {"id": "data:geo:GSE139533", "type": "dataset", "label": "GEO GSE139533"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34238116", "type": "extraction", "used": ["source:pmid:34238116"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE139533", "type": "accession_resolution", "used": ["data:geo:GSE139533"], "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:34238116", "parent_hash": "sha256:cd8df1db5e7ed81a87d20ce4ea06479bc065f5bc300701d95166dd41fbf89057", "fork_of": null, "generation": 5}, "gaps": ["asset:data:geo:GSE139533 licence not read", "asset:data:geo:GSE139533 not downloaded", "asset:data:geo:GSE43378 licence not read", "asset:data:geo:GSE43378 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["as set at P < 0.05. Statistical analysis The IHC results were analyzed in SPSS (version 20.0)", "g the chi-square test. Differences among the IHC scores in each group were determined using a"], "order_basis": "paper_text_order:3219", "id": "assay:1"}, {"role": "analysis", "definition_id": "contingency_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["chi_square_test"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["chi-square"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}