Identification of MCM4 as a Prognostic Marker of Hepatocellular Carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34961841", "kind": "science-record", "revision": 5, "content_hash": "sha256:019a20380870f280cad230edbeb737731f8b379f8ed4342c627fc18050cffb78", "created_at": "2026-11-01T17:36:40Z", "updated_at": "2026-11-01T22:48:08Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of MCM4 as a Prognostic Marker of Hepatocellular Carcinoma.", "doi": "10.1155/2021/7479326", "pmid": "34961841", "authors": ["Huandi Zhou", "Le Jiang", "Guohui Wang", "Linlin Su", "Liubing Hou", "Xiaoying Xue"], "journal": "BioMed research international", "year": 2021, "abstract": "METHODS: MCM4 expression difference in HCC were analyzed from TCGA and GEO data and verified by real-time PCR and western blot. ROC curve was used to analyze the diagnostic value of MCM4 and AFP. Additionally, the relationship between MCM4 and stage or nodal metastasis status or grade or age in TCGA cohort with HCC was observed from the UALCAN website. The univariate and multivariate Cox and functional analyses were done to explore the prognostic value of MCM4 in TCGA cohort.\nRESULTS: It was found that MCM4 was significantly highly expressed in HCC tissues from TCGA, GEO, and experimental data. Furthermore, ROC curve analysis showed that MCM4 was superior to be a diagnostic biomarker than AFP from TCGA (AUCMCM4 = 0.9461, AUCAFP = 0.7056) and GEO (GSE19665: AUCMCM4 = 0.8800, AUCAFP = 0.5100; GSE64041 AUCMCM4 = 0.8038, AUCAFP = 0.6304). AUC of MCM4 from real-time PCR result in 60 pairs of HCC and adjacent tissues was 0.7172, demonstrating the prediction value of MCM4. Besides, different expression tendencies of MCM4 among different stages or nodal metastasis status or grade or age were observed from the UALCAN website. In addition, multiROC analysis showed the advantage of MCM4 as a survival prediction at 1, 3, and 5 years with the higher AUC at 0.69 of 1 year, 0.65 of 3 years, and 0.61 of 5 years. It was shown that MCM4 was independently associated with OS in univariate and multivariate Cox analysis. And GSEA displayed that MCM4 was highly enriched in KEGG_CELL_CYCLE signaling pathway following higher correlation positively with CDC6, PLK1, CRC1, and BUB1B in HCC.\nCONCLUSION: MCM4 might be a potential biomarker in guiding the prognostic status of HCC patients.", "claims": [{"id": "claim-method", "statement": "Cox proportional hazard regression model was used for univariate or multivariate analysis to explore MCM4 independent prognostic role.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34961841", "locator": "sections[11] \"2.9. Statistical Analysis\" paragraph 2", "quote": "Cox proportional hazard regression model was used for univariate or multivariate analysis to explore MCM4 independent prognostic role."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and/or analyzed during the current study are presented in the main file. Additional data are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34961841", "locator": "sections[21] \"Data Availability\" paragraph 2", "quote": "The datasets generated and/or analyzed during the current study are presented in the main file. Additional data are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "ROC curve analysis showed that MCM4 was superior to be a diagnostic biomarker than AFP from TCGA and GEO.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34961841", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Furthermore, ROC curve analysis showed that MCM4 was superior to be a diagnostic biomarker than AFP from TCGA (AUCMCM4 = 0.9461, AUCAFP = 0.7056) and GEO (GSE19665: AUCMCM4 = 0.8800, AUCAFP = 0.5100; GSE64041 AUCMCM4 = 0.8038, AUCAFP = 0.6304)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "ROC curve analysis showed that MCM4 was superior to be a diagnostic biomarker than AFP from TCGA and GEO.", "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:34961841"], "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:GSE19665"], "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:GSE19665"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34961841", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2021/7479326", "sha256": "sha256:7ae3d8c29546581040eb7c863929b36c0dfdfff2eb9ad7ee28957e1a814ea634", "bytes": 37562, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2021/7479326", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8710152", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE19665", "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=GSE19665", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE19665", "version": null, "note": "The datasets generated and/or analyzed during the current study are presented in the main file. Additional data are available from the corresponding author on reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated and/or analyzed during the current study are presented in the main file. Additional data are available from the corresponding author on reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM490987", "GSM490988", "GSM490989", "GSM490990", "GSM490991", "GSM490992", "GSM490993", "GSM490994", "GSM490995", "GSM490996", "GSM490997", "GSM490998", "GSM490999", "GSM491000", "GSM491001", "GSM491002", "GSM491003", "GSM491004", "GSM491005", "GSM491006"], "sample_count": 20, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Aberrant DNA methylation in hepatitis B and C virus-related hepatocellular carcinoma", "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:GSE64041", "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=GSE64041", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE64041", "version": null, "note": "The datasets generated and/or analyzed during the current study are presented in the main file. Additional data are available from the corresponding author on reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated and/or analyzed during the current study are presented in the main file. Additional data are available from the corresponding author on reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2052455", "GSM2052456", "GSM2052457", "GSM2052458", "GSM2052459", "GSM2052460", "GSM2052461", "GSM2052462", "GSM2052463", "GSM2052464", "GSM2052465", "GSM2052466", "GSM2052467", "GSM2052468", "GSM2052469", "GSM2052470", "GSM2052471", "GSM2052472", "GSM2052473", "GSM2052474", "GSM2052475", "GSM2052476", "GSM2052477", "GSM2052478", "GSM2052479", "GSM2052480", "GSM2052481", "GSM2052482", "GSM2052483", "GSM2052484", "GSM2052485", "GSM2052486", "GSM2052487", "GSM2052488", "GSM2052489", "GSM2052490", "GSM2052491", "GSM2052492", "GSM2052493", "GSM2052494", "GSM2052495", "GSM2052496", "GSM2052497", "GSM2052498", "GSM2052499", "GSM2052500", "GSM2052501", "GSM2052502", "GSM2052503", "GSM2052504", "GSM2052505", "GSM2052506", "GSM2052507", "GSM2052508", "GSM2052509", "GSM2052510", "GSM2052511", "GSM2052512", "GSM2052513", "GSM2052514", "GSM2052515", "GSM2052516", "GSM2052517", "GSM2052518", "GSM2052519", "GSM2052520", "GSM2052521", "GSM2052522", "GSM2052523", "GSM2052524", "GSM2052525", "GSM2052526", "GSM2052527", "GSM2052528", "GSM2052529", "GSM2052530", "GSM2052531", "GSM2052532", "GSM2052533", "GSM2052534", "GSM2052535", "GSM2052536", "GSM2052537", "GSM2052538", "GSM2052539", "GSM2052540", "GSM2052541", "GSM2052542", "GSM2052543", "GSM2052544", "GSM2052545", "GSM2052546", "GSM2052547", "GSM2052548", "GSM2052549", "GSM2052550", "GSM2052551", "GSM2052552", "GSM2052553", "GSM2052554", "GSM2052555", "GSM2052556", "GSM2052557", "GSM2052558", "GSM2052559", "GSM2052560", "GSM2052561", "GSM2052562", "GSM2052563", "GSM2052564", "GSM2052565", "GSM2052566", "GSM2052567", "GSM2052568", "GSM2052569", "GSM2052570", "GSM2052571", "GSM2052572", "GSM2052573", "GSM2052574", "GSM2052575", "GSM2052576", "GSM2052577", "GSM2052578", "GSM2052579"], "sample_count": 125, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Gene expression profiling in paired human hepatocellular carcinoma and liver parenchyma biopsies and normal liver biopsies.", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE19665 not downloaded", "asset:data:geo:GSE19665 licence not read", "asset:data:geo:GSE64041 not downloaded", "asset:data:geo:GSE64041 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "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": 1.0, "band": "verbatim", "quote": "Cox proportional hazard regression model was used for univariate or multivariate analysis to explore MCM4 independent prognostic role."}}, {"id": "method-2", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "log-rank"}}, {"id": "method-3", "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": 0.8, "band": "high", "quote": "limma"}}, {"id": "method-4", "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": 0.7, "band": "medium", "quote": "ROC curve"}}], "targets": [], "gaps": []}, "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": ["survival_km"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier."}, "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": ["GSE64041", "GSE19665"], "resolved_accessions": ["GSE64041", "GSE19665"], "statements": ["The datasets generated and/or analyzed during the current study are presented in the main file. Additional data are available from the corresponding author on reasonable request."], "basis": "The paper names GSE64041, GSE19665 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": ["survival_km"], "assets": ["source:pmid:34961841", "data:geo:GSE19665"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE19665"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:13:22Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 12078, "completion_tokens": 2448, "cached_tokens": 256}}, "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:34961841", "type": "paper", "label": "pmid:34961841"}, {"id": "source:pmid:34961841", "type": "manuscript", "label": "PMID 34961841 full text"}, {"id": "data:geo:GSE19665", "type": "dataset", "label": "GEO GSE19665"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34961841", "type": "paper", "label": "pmid:34961841"}, {"id": "source:pmid:34961841", "type": "manuscript", "label": "PMID 34961841 full text"}, {"id": "data:geo:GSE19665", "type": "dataset", "label": "GEO GSE19665"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34961841", "type": "extraction", "used": ["source:pmid:34961841"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE19665", "type": "accession_resolution", "used": ["data:geo:GSE19665"], "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:34961841", "parent_hash": "sha256:ea04c13abf36f681d2997d0ab197a4ccca866e867826a93554e45503f6c8109c", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE19665 licence not read", "asset:data:geo:GSE19665 not downloaded", "asset:data:geo:GSE64041 licence not read", "asset:data:geo:GSE64041 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["lyzed from TCGA and GEO data and verified by real-time PCR and western blot. ROC curve was used to anal", "= 0.8038, AUCAFP = 0.6304). AUC of MCM4 from real-time PCR result in 60 pairs of HCC and adjacent tissu", "rker verified by ROC curve analysis based on real-time PCR experiment data from the 60 pairs of HCC tis", "1 data; (d) ROC curve analysis MCM4 based on real-time PCR experimental data in 60 pairs of HCC and adj"], "order_basis": "paper_text_order:126", "id": "assay:1"}, {"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": ["e ROC curve analysis was assessed in the GEO microarray data (GSE19665 and GSE64041). It showed the"], "order_basis": "paper_text_order:3725", "id": "assay:2"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Cox proportional hazard regression model was used for univariate or multivariate analysis to explore MCM4 independent prognostic role."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}