Pediatric Liver Tumors

Ng, Kenneth H. L.; Mogul, Douglas

doi:10.1016/j.cld.2018.06.008

Cited by 69 publications

(84 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The previous study showed that LIN28B is an oncofetal cancer stem cell-like marker in the recurrence of hepatocellular carcinoma [45]. Hepatocellular carcinoma may have similar molecular mechanisms with hepatoblastoma, such as the activation of the Wnt/β-catenin signaling pathway [46][47][48][49]. Therefore, it was reasonable to investigate the genetic implication of the LIN28B gene in the risk of hepatoblastoma.…”

Section: Discussionmentioning

confidence: 99%

LIN28B gene polymorphisms modify hepatoblastoma susceptibility in Chinese children

et al. 2020

View full text Add to dashboard Cite

Hepatoblastoma is one of the malignant liver tumors in children. However, genetic mechanisms underpinning the initiation of hepatoblastoma remain largely unclear. The previous study showed that lin-28 homolog B (LIN28B) might play a role in the development of hepatoblastoma. To detect the association between LIN28B gene polymorphisms and hepatoblastoma risk in Chinese children, we conducted a five-center case-control study of 275 hepatoblastoma patients and 1018 cancer-free controls. Four potentially functional polymorphisms were genotyped using the Taqman method. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the associations. We found that the rs314276 C>A polymorphism (AA vs. CC: adjusted OR=2.05, 95% CI=1.36-3.10, P=0.0006; AA vs. CA/CC: adjusted OR=2.11, 95% CI=1.43-3.12, P=0.0002) and rs9404590 T>G (GG vs. TT: adjusted OR=1.89, 95% CI=1.20-3.00, P=0.007; GG vs. TT/TG: adjusted OR=1.87, 95% CI=1.20-2.92, P=0.006) were associated with increased hepatoblastoma risk. Combination analysis of risk genotypes showed that patients with four risk genotypes had a higher chance of developing hepatoblastoma than carriers of 1 to 3 risk genotypes. Stratification analysis showed the significant association between the rs314276 AA genotype and hepatoblastoma risk in both age and sex groups, as well as clinical stages III+IV cases. The rs9404590 GG genotype was associated with hepatoblastoma risk in participants' ≥17 months, in females, and for those with clinical stages III+IV disease. Furthermore, four risk genotypes confer higher hepatoblastoma susceptibility in both age and sex groups, as well as groups with clinical stages III+IV disease. Genotype-based gene expression analysis confirmed that the rs9404590 T>G polymorphism was significantly associated with altered LIN28B gene expression. We further validated our findings using false-positive probability analysis. This finding suggested that LIN28B gene polymorphisms may be associated with an increased predisposition to hepatoblastoma.

show abstract

Section: Discussionmentioning

confidence: 99%

LIN28B gene polymorphisms modify hepatoblastoma susceptibility in Chinese children

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In the cirrhotic context, the development of HCC implies both fibrogenetic mechanism and interaction between necro-inflammatory and regenerative events. Nevertheless, only about 30% of pediatric cases of HCC are associated with cirrhosis or pre-existing liver abnormality [ 6 ]. Therefore, it is reasonable to hypothesize that other genetic and epigenetic changes may be involved in pathogenesis of HCC in healthy liver in the pediatric age [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Focal Adhesion Kinase (FAK) Over-Expression and Prognostic Implication in Pediatric Hepatocellular Carcinoma

Francalanci

Giovannoni

Stefanis

et al. 2020

IJMS

View full text Add to dashboard Cite

Focal adhesion kinase (FAK) is over-expressed and is correlated with aggressiveness in adult hepatocellular carcinoma (HCC). Inhibition of FAK decreases HCC invasiveness by down-regulating Enhancer of Zeste homolog 2 (EZH2), an epigenetic controller, that acts in transcriptional repression of a large number of genes via histone 3 methylation of lysine 27 (H3K27me3). Here, we investigated the hepatic expression of total FAK, EZH2, H3K27me3, and proliferating cell nuclear antigen (PCNA) in 17 pediatric HCCs and 8 healthy livers (CTRL). Quantitative imaging analysis showed that FAK gene/protein expression is up-regulated in HCCs compared to CTRL and, among tumor samples the levels of this gene/protein are significantly higher in cirrhotic HCCs than in a healthy milieu. Accordingly, the protein levels of EZH2 were also significantly increased in HCCs from a cirrhotic background. Intriguingly, the protein expression of FAK, EZH2, and PCNA significantly inversely correlated with tumor size. Finally, in HCC samples, mainly in cirrhotic background, the up-regulation of FAK gene positively correlated with that observed in β-Catenin gene. Conclusion: FAK gene/protein is over-expressed in pediatric HCCs concomitantly to EZH2 protein and β-Catenin gene, with a more significant up-regulation in a cirrhotic background. This triad of interactors deserves further investigations for translational application.

show abstract

“…Hepatoblastoma (HB) is the most common malignant liver tumor in children under the age of 4 years and its incidence has increased over the last decades (Kremer et al 2014). Hepatocellular carcinoma (HCC) has also been described in the pediatric population, but the tumor occurs more rarely than HB and predominantly manifest in older children or young adults (Ng and Mogul 2018). Although the survival rates of pediatric HB and HCC have improved up to 80% over the last decades, due to advanced surgical techniques and chemotherapeutic treatments, there are still HB patient subgroups with a dismal prognosis (Tulla et al 2015;Khanna and Verma 2018;Czauderna and Garnier 2018).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of SFRP1 is a protumorigenic event in hepatoblastoma and correlates with beta-catenin mutations

Regel

Eichenmüller

Mahajan

et al. 2020

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

Background Hepatoblastoma (HB) and pediatric hepatocellular carcinoma (HCC) are the most common malignant liver tumors in childhood. Both tumor types exhibit genetic and epigenetic alterations in the WNT/β-catenin signaling pathway, which is a key regulator of liver progenitor cells in embryonic development. The tumors demonstrate a high rate of β-catenin mutations and gene expression changes of several WNT antagonists. However, the role of the WNT inhibitory factor secreted frizzled-related protein 1 (SFRP1) has not been addressed in pediatric liver cancer so far. Results In our study, we investigated the gene expression level, DNA methylation status and functional relevance of SFRP1 in HB cell lines and in pediatric liver tumor patient samples. SFRP1 was downregulated due to DNA promoter methylation in all tested HB cell lines. Overexpression of SFRP1 in HB cell lines diminished tumor cell proliferation, colony formation and migration potential. In addition, the SFRP1-expressing HB cell lines showed reduced WNT/β-catenin signaling pathway activity and decreased expression of WNT target genes. To evaluate the utility of SFRP1 as a biomarker in pediatric liver cancer, we determined the gene expression level and DNA methylation status of SFRP1 in 45 pediatric liver tumor patient samples. The correlation analysis of different clinical parameters and tumor characteristics revealed a significant correlation of reduced SFRP1 expression with the presence of mutant β-catenin. The methylation status of SFRP1 was furthermore associated to a pediatric liver tumor type with HCC-like characteristics, TERT mutations and an older age at diagnosis. Conclusion Altogether, our data demonstrate that the epigenetic suppression of the WNT/β-catenin antagonist SFRP1 has an important impact on the malignant behavior of HB cells. Although SFRP1 methylation is a common event in HCC-like pediatric liver tumors, its potential as a prognostic or diagnostic biomarker needs to be further investigated.

show abstract

Pediatric Liver Tumors

Cited by 69 publications

References 79 publications

LIN28B gene polymorphisms modify hepatoblastoma susceptibility in Chinese children

LIN28B gene polymorphisms modify hepatoblastoma susceptibility in Chinese children

Focal Adhesion Kinase (FAK) Over-Expression and Prognostic Implication in Pediatric Hepatocellular Carcinoma

Downregulation of SFRP1 is a protumorigenic event in hepatoblastoma and correlates with beta-catenin mutations

Contact Info

Product

Resources

About