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

dc.contributor.authorAkbulut, Sami
dc.contributor.authorKucukakcali, Zeynep
dc.contributor.authorSahin, Tevfik Tolga
dc.contributor.authorColak, Cemil
dc.contributor.authorYilmaz, Sezai
dc.date.accessioned2026-04-04T13:31:10Z
dc.date.available2026-04-04T13:31:10Z
dc.date.issued2024
dc.departmentİnönü Üniversitesi
dc.description.abstractBackground: 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. Methods: 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. Results: 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. Conclusions: 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.
dc.description.sponsorshipInonu University Scientific Research Projects Coordination Unit; [TYL-2022-3138]
dc.description.sponsorshipThis study was supported and funded by the Inonu University Scientific Research Projects Coordination Unit (Project code: TYL-2022-3138). We would like to thank all members of the coordination committee for their all support. Financial support was used only for bioinformatic analysis.
dc.identifier.doi10.3390/diagnostics14171925
dc.identifier.issn2075-4418
dc.identifier.issue17
dc.identifier.orcid0000-0002-8044-0297
dc.identifier.orcid0000-0001-7956-9272
dc.identifier.orcid0000-0002-6864-7711
dc.identifier.orcid0000-0001-5406-098X
dc.identifier.orcid0000-0002-9132-6115
dc.identifier.pmid39272711
dc.identifier.scopus2-s2.0-85204132318
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://doi.org/10.3390/diagnostics14171925
dc.identifier.urihttps://hdl.handle.net/11616/108624
dc.identifier.volume14
dc.identifier.wosWOS:001311242300001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherMdpi
dc.relation.ispartofDiagnostics
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250329
dc.subjecthepatocellular carcinoma
dc.subjectgenetics
dc.subjectepigenetics
dc.subjectbioinformatic analysis
dc.subjectbiological behavior
dc.subjectprognosis
dc.titleRole of Epigenetic Factors in Determining the Biological Behavior and Prognosis of Hepatocellular Carcinoma
dc.typeArticle

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