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pmid:29795057

Identification of Biological Targets of Therapeutic Intervention for Hepatocellular Carcinoma by Integrated Bioinformatical Analysis.

Wei Qi Hu · Wei Wang · Di Long Fang · Xue Feng Yin

Medical science monitor : international medical journal of experimental and clinical research · 2018 doi:10.12659/MSM.909290

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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title
Identification of Biological Targets of Therapeutic Intervention for Hepatocellular Carcinoma by Integrated Bioinformatical Analysis.
doi
10.12659/MSM.909290
pmid
29795057
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Wei Qi Hu
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Wei Wang
[2]
Di Long Fang
[3]
Xue Feng Yin
journal
Medical science monitor : international medical journal of experimental and clinical research
year
2018
abstract
BACKGROUND We screened the potential molecular targets and investigated the molecular mechanisms of hepatocellular carcinoma (HCC). MATERIAL AND METHODS Microarray data of GSE47786, including the 40 μM berberine-treated HepG2 human hepatoma cell line and 0.08% DMSO-treated as control cells samples, was downloaded from the GEO database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed; the protein-protein interaction (PPI) networks were constructed using STRING database and Cytoscape; the genetic alteration, neighboring genes networks, and survival analysis of hub genes were explored by cBio portal; and the expression of mRNA level of hub genes was obtained from the Oncomine databases. RESULTS A total of 56 upregulated and 8 downregulated DEGs were identified. The GO analysis results were significantly enriched in cell-cycle arrest, regulation of transcription, DNA-dependent, protein amino acid phosphorylation, cell cycle, and apoptosis. The KEGG pathway analysis showed that DEGs were enriched in MAPK signaling pathway, ErbB signaling pathway, and p53 signaling pathway. JUN, EGR1, MYC, and CDKN1A were identified as hub genes in PPI networks. The genetic alteration of hub genes was mainly concentrated in amplification. TP53, NDRG1, and MAPK15 were found in neighboring genes networks. Altered genes had worse overall survival and disease-free survival than unaltered genes. The expressions of EGR1, MYC, and CDKN1A were significantly increased, but expression of JUN was not, in the Roessler Liver datasets. CONCLUSIONS We found that JUN, EGR1, MYC, and CDKN1A might be used as diagnostic and therapeutic molecular biomarkers and broaden our understanding of the molecular mechanisms of HCC.
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Then, log2fold change (log2FC) was calculated to identify genes with expression-level differences.
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Then, log2fold change (log2FC) was calculated to identify genes with expression-level differences.
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The gene expression profile of GSE47786, based on the platform of GPL10558 (Illumina HumanHT-12 V4.0 expression BeadChip) (Illumina Inc, Santiago, CA, USA) and deposited by Lo et al. [18], were downloaded from the Gene Expression Omnibus (GEO) database in National Center for Biotechnology Information (NCBI, http://www.ncbi.nlm.nih.gov/geo/). A 50 -M stock solution of berberine chloride was prepared in DMSO and the GSE47786 available in this study contained 2 cell samples (GSM1159672 and GSM1159671), including 40 μM berberine-treated HepG2 human hepatoma cell line and 0.08% DMSO-treated cells as control.
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sections[3] "Microarray data information and identification of DEGs" paragraph 2
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The gene expression profile of GSE47786, based on the platform of GPL10558 (Illumina HumanHT-12 V4.0 expression BeadChip) (Illumina Inc, Santiago, CA, USA) and deposited by Lo et al. [18], were downloaded from the Gene Expression Omnibus (GEO) database in National Center for Biotechnology Information (NCBI, http://www.ncbi.nlm.nih.gov/geo/). A 50 -M stock solution of berberine chloride was prepared in DMSO and the GSE47786 available in this study contained 2 cell samples (GSM1159672 and GSM1159671), including 40 μM berberine-treated HepG2 human hepatoma cell line and 0.08% DMSO-treated cells as control.
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The study identified 64 differentially expressed genes in berberine-treated HepG2 cells using |log2FC|≥1.0 and P<0.05, based on reanalyzed GEO dataset GSE47786 (GPL10558), whose two samples were GSM1159672 and GSM1159671.
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A 50 -M stock solution of berberine chloride was prepared in DMSO and the GSE47786 available in this study contained 2 cell samples (GSM1159672 and GSM1159671), including 40 μM berberine-treated HepG2 human hepatoma cell line and 0.08% DMSO-treated cells as control.
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sections[9] "Identification of DEGs in hepatocellular carcinoma cell line" paragraph 2
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In total, 64 DEGs were screened out in HepG2 with berberine-treated compared with control group, in which 56 DEGs were upregulated and 8 DEGs were downregulated by using P<0.05 and |log2FC|≥1.0 as cut-off criterion.
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The gene expression profile of GSE47786, based on the platform of GPL10558 (Illumina HumanHT-12 V4.0 expression BeadChip) (Illumina Inc, Santiago, CA, USA) and deposited by Lo et al. [18], were downloaded from the Gene Expression Omnibus (GEO) database in National Center for Biotechnology Information (NCBI, http://www.ncbi.nlm.nih.gov/geo/).
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sections[3] "Microarray data information and identification of DEGs" paragraph 2
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A 50 -M stock solution of berberine chloride was prepared in DMSO and the GSE47786 available in this study contained 2 cell samples (GSM1159672 and GSM1159671), including 40 μM berberine-treated HepG2 human hepatoma cell line and 0.08% DMSO-treated cells as control.
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The study identified 64 differentially expressed genes in berberine-treated HepG2 cells using |log2FC|≥1.0 and P<0.05, based on reanalyzed GEO dataset GSE47786 (GPL10558), whose two samples were GSM1159672 and GSM1159671.
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Genome-wide analysis of berberine chloride-responsive gene expression in HepG2 liver cell line
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llular carcinoma (HCC). MATERIAL AND METHODS Microarray data of GSE47786, including the 40 μM berber
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:29795057", "kind": "science-record", "revision": 5, "content_hash": "sha256:15ecdca7b5f9a9d4429e535e4d259ed8aa0456e91b97c467f6fe69698c82e7df", "created_at": "2026-11-01T15:40:33Z", "updated_at": "2026-11-01T21:59:50Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Biological Targets of Therapeutic Intervention for Hepatocellular Carcinoma by Integrated Bioinformatical Analysis.", "doi": "10.12659/MSM.909290", "pmid": "29795057", "authors": ["Wei Qi Hu", "Wei Wang", "Di Long Fang", "Xue Feng Yin"], "journal": "Medical science monitor : international medical journal of experimental and clinical research", "year": 2018, "abstract": "BACKGROUND We screened the potential molecular targets and investigated the molecular mechanisms of hepatocellular carcinoma (HCC). MATERIAL AND METHODS Microarray data of GSE47786, including the 40 μM berberine-treated HepG2 human hepatoma cell line and 0.08% DMSO-treated as control cells samples, was downloaded from the GEO database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed; the protein-protein interaction (PPI) networks were constructed using STRING database and Cytoscape; the genetic alteration, neighboring genes networks, and survival analysis of hub genes were explored by cBio portal; and the expression of mRNA level of hub genes was obtained from the Oncomine databases. RESULTS A total of 56 upregulated and 8 downregulated DEGs were identified. The GO analysis results were significantly enriched in cell-cycle arrest, regulation of transcription, DNA-dependent, protein amino acid phosphorylation, cell cycle, and apoptosis. The KEGG pathway analysis showed that DEGs were enriched in MAPK signaling pathway, ErbB signaling pathway, and p53 signaling pathway. JUN, EGR1, MYC, and CDKN1A were identified as hub genes in PPI networks. The genetic alteration of hub genes was mainly concentrated in amplification. TP53, NDRG1, and MAPK15 were found in neighboring genes networks. Altered genes had worse overall survival and disease-free survival than unaltered genes. The expressions of EGR1, MYC, and CDKN1A were significantly increased, but expression of JUN was not, in the Roessler Liver datasets. CONCLUSIONS We found that JUN, EGR1, MYC, and CDKN1A might be used as diagnostic and therapeutic molecular biomarkers and broaden our understanding of the molecular mechanisms of HCC.", "claims": [{"id": "claim-method", "statement": "Then, log2fold change (log2FC) was calculated to identify genes with expression-level differences.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29795057", "locator": "sections[3] \"Microarray data information and identification of DEGs\" paragraph 2", "quote": "Then, log2fold change (log2FC) was calculated to identify genes with expression-level differences."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The gene expression profile of GSE47786, based on the platform of GPL10558 (Illumina HumanHT-12 V4.0 expression BeadChip) (Illumina Inc, Santiago, CA, USA) and deposited by Lo et al. [18], were downloaded from the Gene Expression Omnibus (GEO) database in National Center for Biotechnology Information (NCBI, http://www.ncbi.nlm.nih.gov/geo/). A 50 -M stock solution of berberine chloride was prepared in DMSO and the GSE47786 available in this study contained 2 cell samples (GSM1159672 and GSM1159671), including 40 μM berberine-treated HepG2 human hepatoma cell line and 0.08% DMSO-treated cells as control.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29795057", "locator": "sections[3] \"Microarray data information and identification of DEGs\" paragraph 2", "quote": "The gene expression profile of GSE47786, based on the platform of GPL10558 (Illumina HumanHT-12 V4.0 expression BeadChip) (Illumina Inc, Santiago, CA, USA) and deposited by Lo et al. [18], were downloaded from the Gene Expression Omnibus (GEO) database in National Center for Biotechnology Information (NCBI, http://www.ncbi.nlm.nih.gov/geo/). A 50 -M stock solution of berberine chloride was prepared in DMSO and the GSE47786 available in this study contained 2 cell samples (GSM1159672 and GSM1159671), including 40 μM berberine-treated HepG2 human hepatoma cell line and 0.08% DMSO-treated cells as control."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified 64 differentially expressed genes in berberine-treated HepG2 cells using |log2FC|≥1.0 and P<0.05, based on reanalyzed GEO dataset GSE47786 (GPL10558), whose two samples were GSM1159672 and GSM1159671.", "kind": "quantitative", "target": {"value": 0.08, "unit": "per cent", "tolerance": null, "source": "A 50 -M stock solution of berberine chloride was prepared in DMSO and the GSE47786 available in this study contained 2 cell samples (GSM1159672 and GSM1159671), including 40 μM berberine-treated HepG2 human hepatoma cell line and 0.08% DMSO-treated cells as control."}, "evidence": [{"asset": "source:pmid:29795057", "locator": "sections[9] \"Identification of DEGs in hepatocellular carcinoma cell line\" paragraph 2", "quote": "In total, 64 DEGs were screened out in HepG2 with berberine-treated compared with control group, in which 56 DEGs were upregulated and 8 DEGs were downregulated by using P<0.05 and |log2FC|≥1.0 as cut-off criterion."}, {"asset": "source:pmid:29795057", "locator": "sections[3] \"Microarray data information and identification of DEGs\" paragraph 2", "quote": "The gene expression profile of GSE47786, based on the platform of GPL10558 (Illumina HumanHT-12 V4.0 expression BeadChip) (Illumina Inc, Santiago, CA, USA) and deposited by Lo et al. [18], were downloaded from the Gene Expression Omnibus (GEO) database in National Center for Biotechnology Information (NCBI, http://www.ncbi.nlm.nih.gov/geo/)."}, {"asset": "source:pmid:29795057", "locator": "sections[3] \"Microarray data information and identification of DEGs\" paragraph 2", "quote": "A 50 -M stock solution of berberine chloride was prepared in DMSO and the GSE47786 available in this study contained 2 cell samples (GSM1159672 and GSM1159671), including 40 μM berberine-treated HepG2 human hepatoma cell line and 0.08% DMSO-treated cells as control."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified 64 differentially expressed genes in berberine-treated HepG2 cells using |log2FC|≥1.0 and P<0.05, based on reanalyzed GEO dataset GSE47786 (GPL10558), whose two samples were GSM1159672 and GSM1159671.", "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:29795057"], "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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[18], were downloaded from the Gene Expression Omnibus (GEO) database in National Center for Biotechnology Information (NCBI, http://www.ncbi.nlm.nih.gov/geo/). A 50 -M stock solution of berberine chloride was prepared in DMSO and the GSE47786 available in this study contained 2 cell samples (GSM1159672 and GSM1159671), including 40 μM berberine-treated HepG2 human hepatoma cell line and 0.08% DMSO-treated cells as control.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The gene expression profile of GSE47786, based on the platform of GPL10558 (Illumina HumanHT-12 V4.0 expression BeadChip) (Illumina Inc, Santiago, CA, USA) and deposited by Lo et al. [18], were downloaded from the Gene Expression Omnibus (GEO) database in National Center for Biotechnology Information (NCBI, http://www.ncbi.nlm.nih.gov/geo/). A 50 -M stock solution of berberine chloride was prepared in DMSO and the GSE47786 available in this study contained 2 cell samples (GSM1159672 and GSM1159671), including 40 μM berberine-treated HepG2 human hepatoma cell line and 0.08% DMSO-treated cells as control.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM1159671", "GSM1159672"], "sample_count": 2, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "Genome-wide analysis of berberine chloride-responsive gene expression in HepG2 liver cell line", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE47786 not downloaded", "asset:data:geo:GSE47786 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}, {"id": "method-2", "family": null, "specific": null, "label": "log2 fold change (log2FC)", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Then, log2fold change (log2FC) was calculated to identify genes with expression-level differences."}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "build_graph", "expected_value": 0.08, "unit": "per cent", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. 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MATERIAL AND METHODS Microarray data of GSE47786, including the 40 μM berber"], "order_basis": "paper_text_order:242", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["amino acid phosphorylation, cell cycle, and apoptosis. The KEGG pathway analysis showed that DEGs"], "order_basis": "paper_text_order:1094", "id": "assay:2"}, {"role": "analysis", "definition_id": "network_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["protein-protein interaction"], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}