Comprehensive Analysis of Glycolysis-Related Genes for Prognosis, Immune Features, and Candidate Drug Development in Colon Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34422808", "kind": "science-record", "revision": 8, "content_hash": "sha256:f256e31322eb0ad9e355d67ed9a5930481d33f4495322f71595fa097894b8597", "created_at": "2026-11-01T15:41:48Z", "updated_at": "2026-11-01T22:47:21Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive Analysis of Glycolysis-Related Genes for Prognosis, Immune Features, and Candidate Drug Development in Colon Cancer.", "doi": "10.3389/fcell.2021.684322", "pmid": "34422808", "authors": ["Zhongqi Cui", "Guifeng Sun", "Ramesh Bhandari", "Jiayi Lu", "Mengmei Zhang", "Rajeev Bhandari", "Fenyong Sun", "Zhongchen Liu", "Shasha Zhao"], "journal": "Frontiers in cell and developmental biology", "year": 2021, "abstract": "The dysregulated expression of glycolysis-related genes (GRGs) is closely related to the occurrence of diverse tumors and regarded as a novel target of tumor therapy. However, the role of GRGs in colon cancer is unclear. We obtained 226 differential GRGs (DE-GRGs) from The Cancer Genome Atlas (TCGA) database. Cox regression analysis was used to construct a DE-GRG prognostic model, including P4HA1, PMM2, PGM2, PPARGC1A, PPP2CB, STC2, ENO3, and CHPF2. The model could accurately predict the overall survival rate of TCGA and GSE17536 patient cohorts. The risk score of the model was closely related to a variety of clinical traits and was an independent risk factor for prognosis. Enrichment analysis revealed the activation of a variety of glycolysis metabolism and immune-related signaling pathways in the high-risk group. High-risk patients displayed low expression of CD4+ memory resting T cells and resting dendritic cells and high expression of macrophages M0 compared with the expression levels in the low-risk patients. Furthermore, patients in the high-risk group had a higher tumor mutation load and tumor stem cell index and were less sensitive to a variety of chemotherapeutic drugs. Quantitative reverse transcription polymerase chain reaction and immunohistochemistry analyses validated the expression of eight GRGs in 43 paired clinical samples. This is the first multi-omics study on the GRGs of colon cancer. The establishment of the risk model may benefit the prognosis and drug treatment of patients.", "claims": [{"id": "claim-method", "statement": "Differential glycolysis-related genes in TCGA COAD tumor tissues and adjacent non-tumor tissues with a false discovery rate (FDR) < 0.05 were identified using the limma R package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34422808", "locator": "sections[4] \"Identification of Differential Glycolysis-Related Gene and Function Analyses\" paragraph 2", "quote": "Differential glycolysis-related genes in TCGA COAD tumor tissues and adjacent non-tumor tissues with a false discovery rate (FDR) < 0.05 were identified using the limma R package."}], "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:34422808", "locator": "sections[30] \"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"}], "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:34422808"], "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:GSE17536"], "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:GSE17536"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34422808", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcell.2021.684322", "sha256": "sha256:743f533be884bd8a896dcd7950aa51387322873c5debebfc20e7a44a88e0bd2b", "bytes": 54587, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fcell.2021.684322", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8377503", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE17536", "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=GSE17536", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE17536", "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": ["GSM437093", "GSM437094", "GSM437095", "GSM437096", "GSM437097", "GSM437098", "GSM437099", "GSM437100", "GSM437101", "GSM437102", "GSM437103", "GSM437104", "GSM437105", "GSM437106", "GSM437107", "GSM437108", "GSM437109", "GSM437110", "GSM437111", "GSM437112", "GSM437113", "GSM437114", "GSM437115", "GSM437116", "GSM437117", "GSM437118", "GSM437119", "GSM437120", "GSM437121", "GSM437122", "GSM437123", "GSM437124", "GSM437125", "GSM437126", "GSM437127", "GSM437128", "GSM437129", "GSM437130", "GSM437131", "GSM437132", "GSM437133", "GSM437134", "GSM437135", "GSM437136", "GSM437137", "GSM437138", "GSM437139", "GSM437140", "GSM437141", "GSM437142", "GSM437143", "GSM437144", "GSM437145", "GSM437146", "GSM437147", "GSM437148", "GSM437149", "GSM437150", "GSM437151", "GSM437152", "GSM437153", "GSM437154", "GSM437155", "GSM437156", "GSM437157", "GSM437158", "GSM437159", "GSM437160", "GSM437161", "GSM437162", "GSM437163", "GSM437164", "GSM437165", "GSM437166", "GSM437167", "GSM437168", "GSM437169", "GSM437170", "GSM437171", "GSM437172", "GSM437173", "GSM437174", "GSM437175", "GSM437176", "GSM437177", "GSM437178", "GSM437179", "GSM437180", "GSM437181", "GSM437182", "GSM437183", "GSM437184", "GSM437185", "GSM437186", "GSM437187", "GSM437188", "GSM437189", "GSM437190", "GSM437191", "GSM437192", "GSM437193", "GSM437194", "GSM437195", "GSM437196", "GSM437197", "GSM437198", "GSM437199", "GSM437200", "GSM437201", "GSM437202", "GSM437203", "GSM437204", "GSM437205", "GSM437206", "GSM437207", "GSM437208", "GSM437209", "GSM437210", "GSM437211", "GSM437212", "GSM437213", "GSM437214", "GSM437215", "GSM437216", "GSM437217", "GSM437218", "GSM437219", "GSM437220", "GSM437221", "GSM437222", "GSM437223", "GSM437224", "GSM437225", "GSM437226", "GSM437227", "GSM437228", "GSM437229", "GSM437230", "GSM437231", "GSM437232", "GSM437233", "GSM437234", "GSM437235", "GSM437236", "GSM437237", "GSM437238", "GSM437239", "GSM437240", "GSM437241", "GSM437242", "GSM437243", "GSM437244", "GSM437245", "GSM437246", "GSM437247", "GSM437248", "GSM437249", "GSM437250", "GSM437251", "GSM437252", "GSM437253", "GSM437254", "GSM437255", "GSM437256", "GSM437257", "GSM437258", "GSM437259", "GSM437260", "GSM437261", "GSM437262", "GSM437263", "GSM437264", "GSM437265", "GSM437266", "GSM437267", "GSM437268", "GSM437269"], "sample_count": 177, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Metastasis Gene Expression Profile Predicts Recurrence and Death in Colon Cancer Patients (Moffitt Samples)", "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:34422808:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:65500cd942fa6e607192c57d97d51306f782624f1d0beb2635d1647e726b4d8c", "bytes": 1001, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[1]#T1", "version": null, "note": "Clinical characteristics of the colon cancer patients used in this study.", "structure": {"pmcid": "PMC8377503", "section_index": 17, "section_title": "Results", "row_count": 29, "column_count": 3}, "table": {"label": "TABLE 1", "caption": "Clinical characteristics of the colon cancer patients used in this study.", "rows": [["", "TCGA cohort", "GSE17536"], ["Number of patients", "473", "177"], ["Age in years (median, range)", "69 (31–90)", "66 (26–92)"], ["Gender (%)", "", ""], ["Female", "215 (45.5%)", "81 (45.8%)"], ["Male", "258 (54.5%)", "96 (54.2%)"], ["Grade (%)", "", ""], ["1", "NA", "16 (9.1%)"], ["2", "NA", "133 (75.7%)"], ["3", "NA", "27 (15.3%)"], ["4", "NA", "0 (0%)"], ["Stage (%)", "", ""], ["I", "76 (16.1%)", "24 (13.6%)"], ["II", "177 (37.4%)", "57 (32.2%)"], ["III", "125 (26.4%)", "57 (32.2%)"], ["IV", "62 (13.1%)", "39 (22.0%)"], ["T", "", ""], ["I", "10 (2.11%)", "NA"], ["II", "77 (16.3%)", "NA"], ["III", "307 (64.9%)", "NA"], ["IV", "56 (9.72%)", "NA"], ["M", "", ""], ["M0", "333 (70.4%)", "NA"], ["M1", "62 (13.1%)", "NA"], ["MX", "49 (10.4%)", "NA"], ["N", "", ""], ["N0", "268 (56.7%)", "NA"], ["N1", "103 (21.8%)", "NA"], ["N2", "80 (16.9%)", "NA"]], "row_count": 29, "column_count": 3, "numeric_cells": 35, "header_rows": 1, "locator": "section[17]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:34422808:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b7b28bb8e6d8c88128ecbf309264cab14fc54100dfaf02b542951f836f42cadc", "bytes": 593, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[19]/table-wrap[1]#T2", "version": null, "note": "Glycolysis related genes Multivariate Cox regression results.", "structure": {"pmcid": "PMC8377503", "section_index": 19, "section_title": "Establishment of Protein–Protein Interaction Network and Selection of Prognosis-Related Glycolysis-Related Genes", "row_count": 10, "column_count": 3}, "table": {"label": "TABLE 2", "caption": "Glycolysis related genes Multivariate Cox regression results.", "rows": [["Multivariate cox analysis"], ["GRGs", "HR", "P value"], ["PPP2CB", "0.558(0.338–0.924)", "0.023"], ["PGM2", "0.658(0.384–1.125)", "0.126"], ["PPARGC1A", "0.649(0–430-0.979)", "0.039"], ["EN03", "1.806(1.037–3.146)", "0.037"], ["PMM2", "0.480(0.253–0.910)", "0.025"], ["P4HA1", "2.209(1.593–3.063)", "<0.001"], ["STC2", "1.312(1.057–1.628)", "0.014"], ["CHPF2", "1.747(0.975–3.130)", "0.061"]], "row_count": 10, "column_count": 3, "numeric_cells": 17, "header_rows": 2, "locator": "section[19]/table-wrap[1]#T2"}}], "gaps": ["asset:data:geo:GSE17536 not downloaded", "asset:data:geo:GSE17536 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Differential glycolysis-related genes in TCGA COAD tumor tissues and adjacent non-tumor tissues with a false discovery rate (FDR) < 0.05 were identified using the limma R package."}}, {"id": "method-2", "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-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 analysis"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "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": ["GSE17536"], "resolved_accessions": ["GSE17536"], "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 GSE17536 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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:34422808", "data:geo:GSE17536", "asset:table:pmid:34422808:1", "asset:table:pmid:34422808:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE17536"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:34:11Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 42060, "completion_tokens": 1302, "cached_tokens": 14080}}, "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:34422808", "type": "paper", "label": "pmid:34422808"}, {"id": "source:pmid:34422808", "type": "manuscript", "label": "PMID 34422808 full text"}, {"id": "data:geo:GSE17536", "type": "dataset", "label": "GEO GSE17536"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34422808", "type": "paper", "label": "pmid:34422808"}, {"id": "source:pmid:34422808", "type": "manuscript", "label": "PMID 34422808 full text"}, {"id": "data:geo:GSE17536", "type": "dataset", "label": "GEO GSE17536"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34422808", "type": "extraction", "used": ["source:pmid:34422808"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE17536", "type": "accession_resolution", "used": ["data:geo:GSE17536"], "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:34422808", "parent_hash": "sha256:c20bd2f54cd348f04850d873723f6242b7d50ccfe7349d7eaaf9d25e9ea374de", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE17536 licence not read", "asset:data:geo:GSE17536 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "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": 0.93, "evidence": ["transcription polymerase chain reaction and immunohistochemistry analyses validated the expression of eight G"], "order_basis": "paper_text_order:1350", "id": "assay:1"}, {"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": ["written consent. Cell Culture and Transient Transfection HCT116 and SW480 human CRC cell lines were c", "10% fetal bovine serum (FBS). For transient transfection, prior to the day of transfection 2.5 × 105/", "transient transfection, prior to the day of transfection 2.5 × 105/ml of HTC116 and SW480 cells were", "40 to 60% confluent growth. These cells were transfected with small interfering RNA (siRNA) to STC2 ("], "order_basis": "paper_text_order:2315", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["ient Transfection HCT116 and SW480 human CRC cell lines were cultured at 37°C in a 5% CO2 incubator in Roswell Par"], "order_basis": "paper_text_order:2354", "id": "assay:3"}, {"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": ["Differential glycolysis-related genes in TCGA COAD tumor tissues and adjacent non-tumor tissues with a false discovery rate (FDR) < 0.05 were identified using the limma R package."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}