ArticleEuropean journal of medical research2025
Bioinformatics analysis and experimental studies reveal KPNA2 as a novel biomarker of hepatocellular carcinoma progression and telomere maintenance.
Article in European journal of medical research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed.
- Integrative bioinformatics and machine learning reveal hub genes and immune signatures bridging type 2 diabetes mellitus, fracture susceptibility, and osteoblast differentiation dysfunction.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- A Prognostic Risk Model for Hepatocellular Carcinoma Integrating Ferroptosis and Metabolic Reprogramming Signatures.Journal of Cancer · 2026Article
- Integrative transcriptomic analysis reveals miR-26a-5p downregulation and a potential predictive gene signature for the progression of metabolic liver disease.Frontiers in cell and developmental biology · 2026Article
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Abstract
backgroundTelomere maintenance mechanisms (TMMs) play a distinct role in the initiation and progression of hepatocellular carcinoma (HCC). However, the prognostic relevance of telomere maintenance (TM)-related genes in HCC remains largely unclear.
methodsWe integrated expression profiles of TM-related genes and corresponding clinicopathological data from public databases. Univariate analyses were performed to identify prognostic genes, and Cytoscape software was used to validate hub genes within the TM-related network. A novel prognostic signature was then constructed using the LASSO Cox regression algorithm. Finally, in vitro experiments were conducted to explore the functional roles of the key hub gene KPNA2 in telomere maintenance, tumor growth, and metastasis in HCC.
resultsIn this study, we identified 224 differentially expressed TM-related genes for the first time. Functional enrichment and pathway analyses revealed that these genes were highly involved in telomere-associated pathways, including cell proliferation and cellular senescence. Protein-protein interaction (PPI) analysis identified eight hub TM-related genes (RNASEH2A, KPNA2, AURKB, FOXM1, MKI67, RAD54L, PLK1, and KIF4A), all of which were positively correlated with telomere maintenance. Furthermore, a novel TM-related prognostic signature comprising seven genes (KPNA2, CACNA1B, IRAK1, CDCA8, RGMA, ETS2, and GNE) was developed using the LASSO Cox model. Notably, KPNA2 was identified as both a TM-related hub gene and a component of the prognostic signature. KPNA2 was found to be significantly upregulated in HCC and associated with poor clinical outcomes. Functional assays revealed that KPNA2 knockdown suppressed telomerase activity, inhibited tumor cell proliferation and metastasis, whereas its overexpression produced the opposite effects. Telomerase inhibition partially alleviated the inhibitory effect of KPNA2 overexpression on cell proliferation and migration.
conclusionsThis study identified eight TM-related hub genes with prognostic significance in HCC and established a novel TM-related gene signature. Furthermore, we validated KPNA2 as a key regulator of telomere maintenance and tumor progression in HCC, suggesting it as a potential therapeutic target for improving clinical management of HCC.
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