Aberrantly DNA Methylated-Differentially Expressed Genes and Pathways in Hepatocellular Carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30719129", "kind": "science-record", "revision": 8, "content_hash": "sha256:e52a6a371a52031be99e3cde54eee595447f517af27c594b812884391b16aa78", "created_at": "2026-11-01T15:40:41Z", "updated_at": "2026-11-01T22:00:20Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Aberrantly DNA Methylated-Differentially Expressed Genes and Pathways in Hepatocellular Carcinoma.", "doi": "10.7150/jca.27832", "pmid": "30719129", "authors": ["Changzhou Cai", "Weilin Wang", "Zhenhua Tu"], "journal": "Journal of Cancer", "year": 2019, "abstract": "Background: Methylation plays a significant role in the etiology and pathogenesis of hepatocellular carcinoma (HCC). The aim of the present study is to identify aberrantly methylated-diferentially expressed genes (DEGs) and dysregulated pathways associated with the development of HCC through integrated analysis of gene expression and methylation microarray. Method: Aberrantly methylated-DEGs were identified from gene expression microarrays (GSE62232, GSE74656) and gene methylation microarrays (GSE44909, GSE57958). Functional enrichment and pathway enrichment analyses were performed through the database of DAVID. Protein-protein interaction (PPI) network was established by STRING and visualized in Cytoscape. Subsequently, overall survival (OS) analysis of hub genes was performed by OncoLnc. Finally, we validated the expression level of CDCA5 by quantitative real-time PCR (qRT-PCR) and western blotting, and performed Immunohistochemical experiments utilizing a tissue microarray. Cell growth assay and flow cytometry were behaved to explore the function of CDCA5. Results: Aberrantly methylated-DEGs were enriched in biological process, molecular function, cellular component and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Among them, cell cycle was enriched most frequently, and some terms associated with cancer were enriched, such as p53 signaling pathway, pathways in cancers, PI3K-Akt signaling pathway and AMPK signaling pathway. After survival analysis and validation in TCGA database including methylation and gene expression status, 12 hub genes were identified. Furthermore, the expression level of new gene CDCA5 was validated in HCC cell lines and hepatic normal cell lines through qRT-PCR and western blotting. In additional, immunohistochemistry experiments revealed higher CDCA5 protein expression from HCC tumor tissues compared with paracancer tissues by tissue microarray. Finally, through loss of function, we demonstrated that CDCA5 promoted proliferation by regulating the cell cycle. Conclusions: In summary, the present study implied possible aberrantly methylated-differentially expressed genes and dysregulated pathways in HCC by bioinformatics analysis and experiments, which could be helpful in understanding the molecular mechanisms underlying the development and progression of HCC. Hub genes including CDC20, AURKB, BIRC5, RRM2, MCM2, PTTG1, CDKN2A, NEK2, CENPF, RACGAP1, GNA14 and especially the new gene CDCA5 may serve as biomarkers for diagnosis, treatment and prognosis of HCC.", "claims": [{"id": "claim-method", "statement": "IHC data between groups were compared by Wilcoxon signed-rank test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30719129", "locator": "sections[14] \"Immunohistochemical analysis and statistical analysis\" paragraph 3", "quote": "IHC data between groups were compared by Wilcoxon signed-rank test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The microarray data of GSE62232 included 81 HCC samples and 10 normal liver tissue samples 11.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30719129", "locator": "sections[3] \"Microarray data\" paragraph 2", "quote": "The microarray data of GSE62232 included 81 HCC samples and 10 normal liver tissue samples 11."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "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:30719129"], "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. 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Method: Aberrantly methylated-DEGs were ide", "histochemical experiments utilizing a tissue microarray. Cell growth assay and flow cytometry were b", "s compared with paracancer tissues by tissue microarray. Finally, through loss of function, we demon", "ver tissues was performed utilizing a tissue microarray from National Human Genetic Resources Sharin"], "order_basis": "paper_text_order:403", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["he expression level of CDCA5 by quantitative real-time PCR (qRT-PCR) and western blotting, and performe"], "order_basis": "paper_text_order:923", "id": "assay:2"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["by quantitative real-time PCR (qRT-PCR) and western blotting, and performed Immunohistochemical experimen", "epatic normal cell lines through qRT-PCR and western blotting. In additional, immunohistochemistry experim", "d high levels of CDAC5 protein expression by western blotting in HCC cells (Figure 6B). Finally, as is sho"], "order_basis": "paper_text_order:952", "id": "assay:3"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["qRT-PCR) and western blotting, and performed Immunohistochemical experiments utilizing a tissue microarray. C", "qRT-PCR and western blotting. In additional, immunohistochemistry experiments revealed higher CDCA5 protein ex", ") following the manufacturer's instructions. Immunohistochemical analysis and statistical analysis Immunohist", "tochemical analysis and statistical analysis Immunohistochemical analysis of HCC tissues and adjacent normal"], "order_basis": "paper_text_order:983", "id": "assay:4"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["g a tissue microarray. Cell growth assay and flow cytometry were behaved to explore the function of CDCA"], "order_basis": "paper_text_order:1068", "id": "assay:5"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["HCC cells (HepG2, Hep3B, Huh7 and LM3) were cultured in DMEM (Gibco, Shanghai, China), added with 10", "temperature of 37°C. QSG-7701 and L-02 were cultured in RPMI 1640 (Gibco, Shanghai, China) with the", "d in this study include the human HCC cells (HepG2, Hep3B, Huh7 and LM3) and normal human hepat", "epatic cells (QSG-7701 and L-02). HCC cells (HepG2, Hep3B, Huh7 and LM3) were cultured in DMEM"], "order_basis": "paper_text_order:3132", "id": "assay:6"}, {"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": ["ondition as above. Hep3B and Huh7 cells were transfected with small interfering RNA (siRNA) specific", "were transfected with small interfering RNA (siRNA) specific for CDCA5 (siCDCA5-1: GCAGGGAGCTTA", "GGTGTGCTCCAAACTCA) or corresponding scramble siRNA as negative control (Ribobio, China) using L"], "order_basis": "paper_text_order:3616", "id": "assay:7"}, {"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": ["IHC data between groups were compared by Wilcoxon signed-rank test."], "order_basis": "consumes_earlier_output", "id": "assay:8"}]}