A four-methylated mRNA signature-based risk score system predicts survival in patients with hepatocellular carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30631005", "kind": "science-record", "revision": 8, "content_hash": "sha256:f71abd90d4615101cf309eb584b39a05c09e76b7ef5e37d635a9269e1fce0994", "created_at": "2026-11-01T15:40:40Z", "updated_at": "2026-11-01T22:00:14Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A four-methylated mRNA signature-based risk score system predicts survival in patients with hepatocellular carcinoma.", "doi": "10.18632/aging.101738", "pmid": "30631005", "authors": ["Yu Wang", "Zhiping Ruan", "Sizhe Yu", "Tao Tian", "Xuan Liang", "Li Jing", "Wenyuan Li", "Xiao Wang", "Lcl Xiang", "F X Claret", "Kejun Nan", "Hui Guo"], "journal": "Aging", "year": 2019, "abstract": "Evidence suggests that altered DNA methylation plays a causative role in the pathogenesis of various cancers, including hepatocellular carcinoma (HCC). Thus, methylated differently expressed genes (MDEGs) could potentially serve as biomarkers and therapeutic targets in HCC. In the present study, screening four genomics profiling datasets (GSE62232, GSE84402, GSE73003 and GSE57956) enabled us to identify a total of 148 MDEGs. A signature was then established based on the top four MDEGs (BRCA1, CAD, CDC20 and RBM8A). Taking clinical variables into consideration, we constructed a risk score system consisting of the four-MDEG signature and the patients' clinical features, which was predictive of prognosis in HCC. The prognostic value of the HCC risk score system was confirmed using TCGA HCC samples. The scores were then used to construct a nomogram, performance of which was evaluated using Harrel's concordance index (C-index) and a calibration curve. The signature-based nomogram for prediction of overall survival in HCC patients exhibited good performance and was superior to traditional staging systems (C-index: 0.676 vs 0.629, P< 0.05). We have thus established a novel risk score system that is predictive of prognosis and is a potentially useful guide for personalized treatment of HCC patients.", "claims": [{"id": "claim-method", "statement": "To identify independent predictors of OS in HCC, univariate Cox regression analysis was performed to evaluate the prognostic value of signatures with a threshold value of 0.2. Multivariate Cox regression analyses were conducted using Forward LR.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30631005", "locator": "sections[14] \"Statistical analysis\" paragraph 2", "quote": "To identify independent predictors of OS in HCC, univariate Cox regression analysis was performed to evaluate the prognostic value of signatures with a threshold value of 0.2. Multivariate Cox regression analyses were conducted using Forward LR."}], "state": "complete"}, {"id": "claim-data-access", "statement": "GSE62232, GSE84402, GSE73003 and GSE57956 comprised the training cohort downloaded from the GEO database. The mRNA expression datasets GSE62232 and GSE84402 were calculated using the limma package in R (v 3.5.1). GSE62232 included 81 HCC and 10 normal liver samples, while, GSE84402 included 14 paired HCC and non-tumor samples (Affymetrix Human Genome U133 plus 2.0 platform).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30631005", "locator": "sections[3] \"Identification and enrichment analysis of MDEGs in HCC\" paragraph 2", "quote": "GSE62232, GSE84402, GSE73003 and GSE57956 comprised the training cohort downloaded from the GEO database. The mRNA expression datasets GSE62232 and GSE84402 were calculated using the limma package in R (v 3.5.1). GSE62232 included 81 HCC and 10 normal liver samples, while, GSE84402 included 14 paired HCC and non-tumor samples (Affymetrix Human Genome U133 plus 2.0 platform)."}], "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:30631005"], "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:GSE57956"], "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:GSE57956"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:30631005", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.18632/aging.101738", "sha256": "sha256:737c4bd2ea6c218340a73326aaeef0e1d67c013c2da4bb11a85c759cda1a7670", "bytes": 27084, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.18632/aging.101738", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6339794", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE57956", "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=GSE57956", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE57956", "version": null, "note": "GSE62232, GSE84402, GSE73003 and GSE57956 comprised the training cohort downloaded from the GEO database. The mRNA expression datasets GSE62232 and GSE84402 were calculated using the limma package in R (v 3.5.1). GSE62232 included 81 HCC and 10 normal liver samples, while, GSE84402 included 14 paired HCC and non-tumor samples (Affymetrix Human Genome U133 plus 2.0 platform).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "GSE62232, GSE84402, GSE73003 and GSE57956 comprised the training cohort downloaded from the GEO database. The mRNA expression datasets GSE62232 and GSE84402 were calculated using the limma package in R (v 3.5.1). 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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": ["GSE62232", "GSE84402", "GSE73003", "GSE57956"], "resolved_accessions": ["GSE62232", "GSE84402", "GSE73003", "GSE57956"], "statements": ["GSE62232, GSE84402, GSE73003 and GSE57956 comprised the training cohort downloaded from the GEO database. The mRNA expression datasets GSE62232 and GSE84402 were calculated using the limma package in R (v 3.5.1). GSE62232 included 81 HCC and 10 normal liver samples, while, GSE84402 included 14 paired HCC and non-tumor samples (Affymetrix Human Genome U133 plus 2.0 platform)."], "basis": "The paper names GSE62232, GSE84402, GSE73003, GSE57956 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": ["cox_ph"], "assets": ["source:pmid:30631005", "data:geo:GSE57956", "asset:table:pmid:30631005:1"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE57956"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:13:19Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 20282, "completion_tokens": 2257, "cached_tokens": 572}}, "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:30631005", "type": "paper", "label": "pmid:30631005"}, {"id": "source:pmid:30631005", "type": "manuscript", "label": "PMID 30631005 full text"}, {"id": "data:geo:GSE57956", "type": "dataset", "label": "GEO GSE57956"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:30631005", "type": "paper", "label": "pmid:30631005"}, {"id": "source:pmid:30631005", "type": "manuscript", "label": "PMID 30631005 full text"}, {"id": "data:geo:GSE57956", "type": "dataset", "label": "GEO GSE57956"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-30631005", "type": "extraction", "used": ["source:pmid:30631005"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE57956", "type": "accession_resolution", "used": ["data:geo:GSE57956"], "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:30631005", "parent_hash": "sha256:ca1086eae4a3ebdf673ac75f826c4945224fc86d102c7a5930feb32d7fe22c92", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE57956 licence not read", "asset:data:geo:GSE57956 not downloaded", "asset:data:geo:GSE62232 licence not read", "asset:data:geo:GSE62232 not downloaded", "asset:data:geo:GSE73003 licence not read", "asset:data:geo:GSE73003 not downloaded", "asset:data:geo:GSE84402 licence not read", "asset:data:geo:GSE84402 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": ["To identify independent predictors of OS in HCC, univariate Cox regression analysis was performed to evaluate the prognostic value of signatures with a threshold value of 0.2. Multivariate Cox regression analyses were conducted using Forward LR."], "order_basis": "analysis_only", "id": "assay:1"}]}