DNA methylation biomarkers for hepatocellular carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30245591", "kind": "science-record", "revision": 7, "content_hash": "sha256:624256d2d56de3ba31b7f36a62f134f9e6d27a0a56357025715d92d51d5e7735", "created_at": "2026-11-01T15:40:37Z", "updated_at": "2026-11-01T22:00:03Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "DNA methylation biomarkers for hepatocellular carcinoma.", "doi": "10.1186/s12935-018-0629-5", "pmid": "30245591", "authors": ["Guorun Fan", "Yaqin Tu", "Cai Chen", "Haiying Sun", "Chidan Wan", "Xiong Cai"], "journal": "Cancer cell international", "year": 2018, "abstract": "BACKGROUND: Aberrant methylation of DNA is a key driver of hepatocellular carcinoma (HCC). In this study, we sought to integrate four cohorts profile datasets to identify such abnormally methylated genes and pathways associated with HCC.\nMETHODS: To this end, we downloaded microarray datasets examining gene expression (GSE84402, GSE46408) and gene methylation (GSE73003, GSE57956) from the GEO database. Abnormally methylated differentially expressed genes (DEGs) were sorted and pathways were analyzed. The String database was then used to perform enrichment and functional analysis of identified pathways and genes. Cytoscape software was used to create a protein-protein interaction network, and MCODE was used for module analysis. Finally, overall survival analysis of hub genes was performed by the OncoLnc online tool.\nRESULTS: In total, we identified 19 hypomethylated highly expressed genes and 14 hypermethylated lowly expressed genes at the screening step, and finally found six mostly changed hub genes including MAD2L1, CDC20, CCNB1, CCND1, AR and ESR1. Pathway analysis showed that aberrantly methylated-DEGs mainly associated with the cell cycle process, p53 signaling, and MAPK signaling in HCC. After validation in TCGA database, the methylation and expression status of hub genes was significantly altered and same with our results. Patients with high expression of MAD2L1, CDC20 and CCNB1 and low expression of CCND1, AR, and ESR1 was associated with shorter overall survival.\nCONCLUSIONS: Taken together, we have identified novel aberrantly methylated genes and pathways linked to HCC, potentially offering novel insights into the molecular mechanisms governing HCC progression and serving as novel biomarkers for precision diagnosis and disease treatment.", "claims": [{"id": "claim-method", "statement": "The threshold was adjusted to cox P value < 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30245591", "locator": "sections[13] \"The relationship between hub genes and the survival in hepatocellular carcinoma\" paragraph 2", "quote": "The threshold was adjusted to cox P value < 0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and/or analysed during the current study are available in the GEO repository, https://www.ncbi.nlm.nih.gov/geo/.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30245591", "locator": "sections[21] \"Availability of data and materials\" paragraph 2", "quote": "The datasets generated and/or analysed during the current study are available in the GEO repository, https://www.ncbi.nlm.nih.gov/geo/."}], "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:30245591"], "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:GSE46408"], "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:GSE46408"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:30245591", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12935-018-0629-5", "sha256": 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expression", "< 2.2e−16"], ["CDC20", "Hypomethylation", "6.12e−13", "High expression", "< 2.2e−16"], ["CCNB1", "Hypomethylation", "2.87e−5", "High expression", "< 2.2e−16"], ["Hypermethylation/low-expression"], ["CCND1", "Hypermethylation", "1.27e−5", "Low expression", "1.27e−5"], ["AR", "Hypermethylation", "2.96e−4", "Low expression", "1.47e−9"], ["ESR1", "Hypermethylation", "0.0258", "Low expression", "< 2.2e−16"]], "row_count": 9, "column_count": 5, "numeric_cells": 13, "header_rows": 1, "locator": "section[12]/table-wrap[1]#Tab3"}}, {"id": "asset:table:pmid:30245591:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:3d204874a95fbe614eae9241459552790564f38057fd1f199f6bfb1ecda17317", "bytes": 2190, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#Tab1", "version": null, "note": "Gene ontology analysis of aberrantly methylated-differentially expressed genes in hepatocellular carcinoma", "structure": {"pmcid": "PMC6142709", "section_index": 10, "section_title": "Gene ontology and pathway functional enrichment analysis", "row_count": 31, "column_count": 5}, "table": {"label": "Table 1", "caption": "Gene ontology analysis of aberrantly methylated-differentially expressed genes in hepatocellular carcinoma", "rows": [["Category", "ID", "Term", "Gene count", "False discovery rate"], ["Hypomethylation and high expression"], ["BP", "GO.0051983", "Regulation of chromosome segregation", "13", "3.94E−20"], ["BP", "GO.0030071", "Regulation of mitotic metaphase/anaphase transition", "12", "4.44E−20"], ["BP", "GO.0007094", "Mitotic spindle assembly checkpoint", "11", "1.30E−19"], ["BP", "GO.0007088", "Regulation of mitotic nuclear division", "14", "3.88E−19"], ["BP", "GO.0010564", "Regulation of cell cycle process", "17", "2.77E−15"], ["CC", "GO.0000793", "Condensed chromosome", "10", "3.89E−10"], ["CC", 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"note": "KEGG pathway analysis of aberrantly methylated-differentially expressed genes in hepatocellular carcinoma", "structure": {"pmcid": "PMC6142709", "section_index": 10, "section_title": "Gene ontology and pathway functional enrichment analysis", "row_count": 13, "column_count": 5}, "table": {"label": "Table 2", "caption": "KEGG pathway analysis of aberrantly methylated-differentially expressed genes in hepatocellular carcinoma", "rows": [["Pathway ID", "Pathway name", "Gene count", "False discovery rate", "Genes"], ["Hypomethylation and high expression"], ["4110", "Cell cycle", "12", "1.03E−15", "ANAPC10, ANAPC4, BUB1, BUB1B, BUB3, CCNB1, CDC16, CDC20, CDC23, MAD1L1, MAD2L1, PTTG1"], ["4114", "Oocyte meiosis", "10", "6.60E−13", "ANAPC10, ANAPC4, AURKA, BUB1, CCNB1, CDC16, CDC20, CDC23, MAD2L1, PTTG1"], ["4914", "Progesterone-mediated oocyte maturation", "8", "1.84E−10", "ANAPC10, ANAPC4, BUB1, CCNB1, CDC16, CDC23, MAD1L1, MAD2L1"], ["4120", "Ubiquitin mediated proteolysis", "6", 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