Role of Epigenetic Factors in Determining the Biological Behavior and Prognosis of Hepatocellular Carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39272711", "kind": "science-record", "revision": 4, "content_hash": "sha256:8387f8aba075d851e48ae030142d7693b5d12f52133cb61d789b170886fb0d73", "created_at": "2026-11-01T20:29:26Z", "updated_at": "2026-11-01T22:55:10Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Role of Epigenetic Factors in Determining the Biological Behavior and Prognosis of Hepatocellular Carcinoma.", "doi": "10.3390/diagnostics14171925", "pmid": "39272711", "authors": ["Sami Akbulut", "Zeynep Kucukakcali", "Tevfik Tolga Sahin", "Cemil Colak", "Sezai Yilmaz"], "journal": "Diagnostics (Basel, Switzerland)", "year": 2024, "abstract": "BACKGROUND: The current study's objective is to evaluate the molecular genetic mechanisms influencing the biological behavior of hepatocellular carcinoma (HCC) by analyzing the transcriptomic and epigenetic signatures of the tumors.\nMETHODS: Transcriptomic data were downloaded from the NCBI GEO database. We investigated the expression differences between the GSE46444 (48 cirrhotic tissues versus 88 HCC tissues) and GSE63898 (168 cirrhotic tissues versus 228 HCC tissues) data sets using GEO2R. Differentially expressed genes were evaluated using GO and KEGG metabolic pathway analysis websites. Whole genome bisulfite sequencing (WGBS) and Methylated DNA Immunoprecipitation Sequencing (MeDIP-Seq) data sets (26 HCC tissues versus 26 adjacent non-tumoral tissues) were also downloaded from the NCBI SRA database. These data sets were analyzed using Bismark and QSEA, respectively. The methylation differences between the groups were assessed using functional enrichment analysis.\nRESULTS: In the GSE46444 data set, 80 genes were upregulated, and 315 genes were downregulated in the tumor tissue (HCC tissue) compared to the non-tumor cirrhotic tissue. In the GSE63898 data set, 1261 genes were upregulated, and 458 genes were downregulated in the cirrhotic tissue compared to the tumor tissues. WGBS revealed that 20 protein-coding loci were hypermethylated. while the hypomethylated regions were non-protein-coding. The methylated residues of the tumor tissue, non-tumorous cirrhotic tissue, and healthy tissue were comparable. MeDIP-Seq, conducted on tumoral and non-tumoral tissues, identified hypermethylated or hypomethylated areas as protein-coding regions. The functional enrichment analysis indicated that these genes were related to pathways including peroxisome, focal adhesion, mTOR, RAP1, Phospholipase D, Ras, and PI3K/AKT signal transduction.\nCONCLUSIONS: The investigation of transcriptomic and epigenetic mechanisms identified several genes significant in the biological behavior of HCC. These genes present potential targets for the development of targeted therapy.", "claims": [{"id": "claim-method", "statement": "The genes that were expressed differently between the “GSE46444” and “GSE63898” data sets were determined using the limma v3.52.4 [32] package (limma v3.52.4) (fold change, log2FC > 1, p < 0.05, Benjamini and Hochberg False Discovery Rate).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39272711", "locator": "sections[5] \"2.1.2. Transcriptome Profiling with Microarrays\" paragraph 2", "quote": "The genes that were expressed differently between the “GSE46444” and “GSE63898” data sets were determined using the limma v3.52.4 [32] package (limma v3.52.4) (fold change, log2FC > 1, p < 0.05, Benjamini and Hochberg False Discovery Rate)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data sets analyzed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39272711", "locator": "sections[20] \"Data Availability Statement\" paragraph 2", "quote": "The data sets analyzed during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The limma-based analysis of GSE46444 identified 80 upregulated and 315 downregulated genes in HCC tissue compared with non-tumor cirrhotic tissue.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39272711", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In the GSE46444 data set, 80 genes were upregulated, and 315 genes were downregulated in the tumor tissue (HCC tissue) compared to the non-tumor cirrhotic tissue."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The limma-based analysis of GSE46444 identified 80 upregulated and 315 downregulated genes in HCC tissue compared with non-tumor cirrhotic tissue.", "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:39272711"], "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:GSE46444"], "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:GSE46444"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39272711", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/diagnostics14171925", "sha256": 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