ArticleJournal of translational medicine2025
HCV-related hepatocellular carcinoma: gene signatures associated with TERT promoter mutations and sex.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- The Prevalence and Clinical Significance of the Centromere Protein-F-Like Immunofluorescence Staining Pattern in a Large ANA-positive Cohort.Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2026Article
- Optimized digital polymerase chain reaction enables detection of telomerase reverse transcriptase C228T mutation for prognostic assessment in hepatocellular carcinoma.World journal of gastrointestinal oncology · 2025Article
- Construction of a novel ferroptosis-related long non-coding RNAs model for predicting prognosis and tumor immune microenvironment in endometrial cancer.Annals of translational medicine · 2025Article
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13 authors.
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Abstract
backgroundHepatocellular carcinoma (HCC) is a rapidly progressing disease, frequently caused by hepatitis C virus (HCV) infection and a higher prevalence in males than females. Over 60% of HCCs harbour frequent activating mutations in the telomerase reverse transcriptase promoter (TERTp). However, the relationship between TERTp status, sex, and expression of specific genes remains poorly understood.
methodsWe conducted a literature search to identify genes that were significantly upregulated in HCV-related HCC, compared to the respective peri-tumour tissues, in at least two independent studies. We identified 90 genes and validated their expression in 59 matched HCV-related HCC and peri-tumour tissues using a custom multiplex array qPCR. HCV-related HCC patients were stratified by TERTp mutations and sex. Statistical analysis was performed to identify relationships between different variables.
resultsOverall, validation analysis confirmed the upregulation of 39 out of 90 genes. Expression levels of 24 genes differed significantly between HCV-related HCC with mutant and wild type TERTp. The expression of FASTK and FLVCR1 genes correlated with TNM and tumour size (p < 0.05). High expression of NUCKS1 was associated with mortality, particularly in male patients. Overall, the expression of 57 genes was sex-linked, with 26 and 48 genes significantly overexpressed in males and in females, respectively, some of which were also associated with mutant TERTp status.
conclusionsWe identified unique molecular signatures in TERTp mutant HCC associated with the activation of specific genes. Such results suggest that TERTp mutant HCC might represent a distinct clinical entity. Furthermore, the up-regulation of several genes in HCV-related HCC is sex-linked. These results are crucial for understanding the mechanisms underlying TERTp mutations in tumour progression and sex-related HCC risk and for developing more effective diagnostic and prognostic biomarkers.
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