Genomics of Viral Hepatitis-Associated Liver Tumors

Péneau, Camille; Zucman‐Rossi, Jessica; Nault, Jean‐Charles

doi:10.3390/jcm10091827

Cited by 11 publications

(9 citation statements)

References 123 publications

(185 reference statements)

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“…The molecular mechanism of TLK2 upregulation in HBVrelated HCC is not clear. Existing studies have shown that CIN is often observed in HBV-related HCC, which is associated with insertional mutations and the activation of cancer driver genes due to HBV DNA randomly integration into the host genome (Guichard et al, 2012;Seeger and Mason, 2015;Péneau et al, 2021). Highly genome-unstable tumors tended to overexpress TLK2 to achieve immune escape through suppressing cGAS-STRING-TBK1-mediated innate immune response (Segura-Bayona et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of tousled-like kinase 2 predicts poor prognosis in HBV-related hepatocellular carcinoma patients after radical resection

Liu,

Lu,

et al. 2024

Front. Genet.

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Background: Tousled-like kinase 2 (TLK2) is integral to DNA repair, replication, and cell cycle regulation, crucial for maintaining genome stability and integrity. However, the expression and prognostic value of TLK2 in hepatitis B viral (HBV) -related hepatocellular carcinoma (HCC) remains unclear.Methods: We examined TLK2 expression and prognostic implications in pan-cancer by using diverse databases. Subsequently, TLK2 expression in HBV-related HCC tissues and adjacent tissues was assessed using quantitative real-time PCR and immunohistochemistry. The prognostic value of TLK2 was assessed through ROC curves, time-dependent ROC curves, Cox regression, Kaplan-Meier curve, and decision curve analysis. Additionally, analyses of immune infiltration, protein-protein interactions, key molecules of tumor-related signaling pathways, molecular subtypes, and TLK2-associated differentially expressed genes (DEGs) were conducted, along with GO/KEGG and GSEA enrichment analyses.Results: TLK2 expression was significantly higher in HCC tissues compared to adjacent tissues and correlated with gender, AFP levels, albumin-bilirubin (ALBI) grade, microvascular invasion (MVI), maximum tumor diameter, tumor number, and TNM stage. TLK2 overexpression emerged as an independent risk factor for overall survival (OS) and recurrence-free survival (RFS) in HBV-related HCC patients. An integrated OS nomogram model, incorporating TLK2, age, ALBI grade, MVI, and tumor number, displayed enhanced prognostic capability (C-index: 0.765, 95% CI: 0.732–0.798) in predicting OS and has a higher net benefit than the TNM stage. Moreover, TLK2 expression correlated closely with immune cell infiltration and key molecules of signaling pathways. Functional enrichment analyses highlighted significant associations with DNA duplex unwinding, double-strand break repair, DNA replication, cell cycle, E2F targets, G2M checkpoint, and MYC targets V1.Conclusion: TLK2 is notably overexpressed in HBV-related HCC and emerges as a promising prognostic biomarker, necessitating further validation.

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Section: Discussionmentioning

confidence: 99%

Overexpression of tousled-like kinase 2 predicts poor prognosis in HBV-related hepatocellular carcinoma patients after radical resection

Liu,

Lu,

et al. 2024

Front. Genet.

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“…HBV/HCV infections can induce genetic instability and have been shown to be important risk factors for HCC 27 , 28 . Several studies have suggested associations between serum FCN3 and FCN2 levels with HCV and HBV infections in patients with HCC 29 , 30 .…”

Section: Discussionmentioning

confidence: 99%

Loss of ficolin-3 expression is associated with poor prognosis in patients with hepatocellular carcinoma

Chen¹,

Yu²,

Wu³

et al. 2023

Int. J. Med. Sci.

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Background: Ficolin-3 (FCN3) is a well-known circulating pattern recognition molecule which plays a role in host immune responses to cancer via activation of the lectin complement pathway. Nevertheless, the clinical significance of FCN3 in patients with hepatocellular carcinoma (HCC) is unclear. Methods: Eighty-seven HCC patients who received hepatectomy at our hospital were included. Immunohistochemical staining was used to assess the FCN3 expression in both tumorous and non-tumorous tissues from the patients, who were classified into high and low expression groups. Differences in clinicopathological characteristics between the two groups were then analyzed. Results: Survival was significantly associated with FCN3 immunohistochemical score (p for trend = 0.048). Kaplan-Meier analysis revealed a higher overall survival rate in the patients with a high FCN3 expression than in those with a low FCN3 expression (p=0.031). A high FCN3 expression in tumor tissue was independently associated with better overall survival (p=0.042). However, multivariate analysis showed that FCN3 expression was not an independent risk factor for overall survival. Conclusion: Our findings suggest that FCN3 is significantly related to the prognosis of HCC. FCN3 may be a prognostic marker in patients with HCC.

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“…First, the integrated AAV sequence typically comprises transcription factor binding sites as well as viral enhancers [91], which causes an oncogene to be strongly overexpressed nearby (CCNE1 or TERT) [44,92]. Second, due to the usage of an alternate transcription start site (TSS) or the viral poly-A site, integrated viral sequences may cause the synthesis of truncated transcripts (for integrations in CCNA2 and TNFSF10, respectively) [93]. Remarkably, a region common to all inserted AAV sequences has recently been identified as a liver-specific enhancer-promoter element [91].…”

Section: Aav Infection and Hepatocellular Carcinomamentioning

confidence: 99%

Adeno-associated virus infection and its impact in human health: an overview

Sant’Anna

Araújo

2022

Virol J

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Discovered as a contaminant of adenovirus stocks in the 1960s, adeno-associated virus (AAV) is a mono-stranded DNA virus that depends on helper factors to replicate. Even though AAV is endemic in the human population (35–80%), it is remarkable that many issues concerning the natural infection by this virus remain unanswered. In this study, we reflect on the main basic aspects of AAV biology and provide an overview of the studies exploring the impact of AAV infection on human health, focusing on three major research areas including, (i) cervical and (ii) liver cancer, and (iii) reproductive system disorders. Conflicting results have been obtained into the association of AAV infection with the occurrence of adverse reproductive outcomes, such as placental complications, spontaneous abortion, and fertility disorders, or with a protective role in HPV-related cervical carcinogenesis. Noteworthy, recent reports have identified AAV insertional mutagenesis as a novel risk factor for the development of hepatocellular carcinoma. This latest finding raises concern regarding the widespread usage of AAV vectors in liver-targeted gene therapy.

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Genomics of Viral Hepatitis-Associated Liver Tumors

Cited by 11 publications

References 123 publications

Overexpression of tousled-like kinase 2 predicts poor prognosis in HBV-related hepatocellular carcinoma patients after radical resection

Overexpression of tousled-like kinase 2 predicts poor prognosis in HBV-related hepatocellular carcinoma patients after radical resection

Loss of ficolin-3 expression is associated with poor prognosis in patients with hepatocellular carcinoma

Adeno-associated virus infection and its impact in human health: an overview

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