Methylation and Expression of the Exercise-Related TLR1 Gene Is Associated With Low Grade Glioma Prognosis and Outcome.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34869584", "kind": "science-record", "revision": 5, "content_hash": "sha256:ffea1ddcce8b859a884082d1f9e4b3f44b56b3fa07d9723e9d864449def38ab5", "created_at": "2026-11-01T17:36:34Z", "updated_at": "2026-11-01T22:48:00Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Methylation and Expression of the Exercise-Related TLR1 Gene Is Associated With Low Grade Glioma Prognosis and Outcome.", "doi": "10.3389/fmolb.2021.747933", "pmid": "34869584", "authors": ["Lichun Lu", "Yifang Hu", "Chen Wang", "Feng Jiang", "Chuyan Wu"], "journal": "Frontiers in molecular biosciences", "year": 2021, "abstract": "Background: Exercise improves function, reduces disability, maintains independence, and improves quality of life for low-grade glioma (LGG) patients. Exercise can also improve the effectiveness of cancer treatment. The goal of this research was to find potential exercise related genes that may be used to predict exercise levels and may be used as a biomarker for cancer outcomes. Methods: The GSE111551 database was thoroughly examined in this research, and the resulting conclusion of exercise-related genes was reached. The protein interaction network (PPI) was used to examine the differentially expressed genes (DEGs). Then the exercise-related gene TLR1 was chosen. The expression, methylation degree, prognosis, and immune relevance of TLR1 were investigated using bioinformatics. In addition, we verified the role of TLR1 in Glioma cell lines. Results: LGG patients with reduced TLR1 expression and hypermethylation had a better overall survival (OS) and progression free survival (PFS), using the TCGA database. Low TLR1 expression and hypermethylation of TLR1 were found to be independent biomarkers for OS using Cox regression. Furthermore, the CGGA database was used to confirm the prognostic function of TLR1 in this cancer. Finally, most methylation sites of TLR1 were strongly correlated with immune infiltration and immune checkpoint. Then, reducing TLR1 expression substantially slowed the cell cycle and decreased LGG cell proliferation, emigration, and infiltration in vitro. Conclusions: Exercise-related gene TLR1 has the potential to be a useful prognostic biomarker, and it is thought to be involved in immune cell infiltration and immunotherapy in LGG.", "claims": [{"id": "claim-method", "statement": "The Kaplan-Meier survival analysis was used to demonstrate the survival link between the high-risk and low-risk groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34869584", "locator": "sections[5] \"Survival Analysis of Gene Expression and Methylation Sites Using TCGA-Low-Grade Glioma Dataset\" paragraph 2", "quote": "The Kaplan-Meier survival analysis was used to demonstrate the survival link between the high-risk and low-risk groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34869584", "locator": "sections[23] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Exercise-related gene TLR1 has the potential to be a useful prognostic biomarker, and it is thought to be involved in immune cell infiltration and immunotherapy in LGG.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34869584", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Exercise-related gene TLR1 has the potential to be a useful prognostic biomarker, and it is thought to be involved in immune cell infiltration and immunotherapy in LGG."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Exercise-related gene TLR1 has the potential to be a useful prognostic biomarker, and it is thought to be involved in immune cell infiltration and immunotherapy in LGG.", "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:34869584"], "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:GSE111551"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "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:GSE111551"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34869584", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fmolb.2021.747933", "sha256": "sha256:079a58fdc6403b170bb5a61002006d4b31fb30b81858892a24e49f91bdb11004", "bytes": 42792, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fmolb.2021.747933", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8635206", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE111551", "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=GSE111551", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE111551", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3034037", "GSM3034038", "GSM3034039", "GSM3034040", "GSM3034041", "GSM3034042", "GSM3034043", "GSM3034044", "GSM3034045", "GSM3034046", "GSM3034047", "GSM3034048", "GSM3034049", "GSM3034050", "GSM3034051", "GSM3034052", "GSM3034053", "GSM3034054", "GSM3034055", "GSM3034056", "GSM3034057", "GSM3034058", "GSM3034059", "GSM3034060", "GSM3034061", "GSM3034062"], "sample_count": 26, "group_sizes": null, "group_sizes_basis": null, "platform": "17586", "taxon": "Homo sapiens", "title": "Blood and skeletal muscle gene signatures of exercise training in men (Muscle data set)", "resolution_checked_at": "2026-11-01T17:30:42Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE111551 not downloaded", "asset:data:geo:GSE111551 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The Kaplan-Meier survival analysis was used to demonstrate the survival link between the high-risk and low-risk groups."}}, {"id": "method-2", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Kaplan-Meier"}}, {"id": "method-3", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.7, "band": "medium", "quote": "Cox regression"}}, {"id": "method-4", "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": "PPI"}}, {"id": "method-5", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "GO enrichment"}}, {"id": "method-6", "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"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor", "method.group_comparison_wilcoxon"]}, "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": false, "required_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: wilcoxon."}, "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": ["GSE111551"], "resolved_accessions": ["GSE111551"], "statements": ["The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors."], "basis": "The paper names GSE111551 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": [], "assets": ["source:pmid:34869584", "data:geo:GSE111551"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "group_comparison_wilcoxon", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE111551"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:10:08Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 12908, "completion_tokens": 1951, "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:34869584", "type": "paper", "label": "pmid:34869584"}, {"id": "source:pmid:34869584", "type": "manuscript", "label": "PMID 34869584 full text"}, {"id": "data:geo:GSE111551", "type": "dataset", "label": "GEO GSE111551"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34869584", "type": "paper", "label": "pmid:34869584"}, {"id": "source:pmid:34869584", "type": "manuscript", "label": "PMID 34869584 full text"}, {"id": "data:geo:GSE111551", "type": "dataset", "label": "GEO GSE111551"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34869584", "type": "extraction", "used": ["source:pmid:34869584"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE111551", "type": "accession_resolution", "used": ["data:geo:GSE111551"], "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:34869584", "parent_hash": "sha256:2f9fe9e2a98031ee47c363cb3817efa31609737ae2252168fc86982c23ff96f1", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE111551 licence not read", "asset:data:geo:GSE111551 not downloaded", "execution.not_run", "method.group_comparison_wilcoxon", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:group_comparison_wilcoxon"], "assays": [{"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["te Cox regression analyses. Cell Culture and Transfection Glioma cell lines (NHA, A172, U87, U251, T98", "into cells at a concentration of 50 nM. The transfected cells were harvested at 24 h after transfect", "ansfected cells were harvested at 24 h after transfection. Statistical Analysis The value of the risk"], "order_basis": "paper_text_order:2474", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["(Gibco, Gaithersburg, MD, United States) was cultured with 10% fetal bovine serum (HyClone, Logan, Unit"], "order_basis": "paper_text_order:2675", "id": "assay:2"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The Kaplan-Meier survival analysis was used to demonstrate the survival link between the high-risk and low-risk groups."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}