Early-onset liver cancer in South America associates with low hepatitis B virus DNA burden

Marchio, Agnès; Cerapio, Juan Pablo; Ruíz, Eloy; Cano, Luis; Casavilca, Sandro; Terris, Benoı̂t; Deharo, Eric; Dejean, Anne; Bertani, Stéphane; Pineau, Pascal

doi:10.1038/s41598-018-30229-8

Cited by 31 publications

(29 citation statements)

References 38 publications

(46 reference statements)

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“…S7, Table S6). This has been observed in independent studies [90–92], suggesting that HBV replication is less active in tumours. Strikingly, tumour samples expressed SP13 at significantly higher proportions of HBV RNAs than other samples except for PVTT ( and S5, Wilcoxon rank sum tests, Bonferroni–Holm adjusted P value <0.05).…”

Section: Resultssupporting

confidence: 68%

Quantitative analysis of the splice variants expressed by the major hepatitis B virus genotypes

et al. 2021

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Hepatitis B virus (HBV) is a major human pathogen that causes liver diseases. The main HBV RNAs are unspliced transcripts that encode the key viral proteins. Recent studies have shown that some of the HBV spliced transcript isoforms are predictive of liver cancer, yet the roles of these spliced transcripts remain elusive. Furthermore, there are nine major HBV genotypes common in different regions of the world, these genotypes may express different spliced transcript isoforms. To systematically study the HBV splice variants, we transfected human hepatoma cells, Huh7, with four HBV genotypes (A2, B2, C2 and D3), followed by deep RNA-sequencing. We found that 13–28 % of HBV RNAs were splice variants, which were reproducibly detected across independent biological replicates. These comprised 6 novel and 10 previously identified splice variants. In particular, a novel, singly spliced transcript was detected in genotypes A2 and D3 at high levels. The biological relevance of these splice variants was supported by their identification in HBV-positive liver biopsy and serum samples, and in HBV-infected primary human hepatocytes. Interestingly the levels of HBV splice variants varied across the genotypes, but the spliced pregenomic RNA SP1 and SP9 were the two most abundant splice variants. Counterintuitively, these singly spliced SP1 and SP9 variants had a suboptimal 5′ splice site, supporting the idea that splicing of HBV RNAs is tightly controlled by the viral post-transcriptional regulatory RNA element.

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Section: Resultssupporting

confidence: 68%

Quantitative analysis of the splice variants expressed by the major hepatitis B virus genotypes

et al. 2021

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“…AFB1, often present in staple foods of populations living in SSA, is known to induce a specific G>T mutation (in exon 7, nucleotide 747, hg38 position on Chr17: 7674216), changing an arginine for a serine at codon 249 of the p53 protein (TP53 R249S) [6]. This specific mutation is frequently found in tumor DNA from patients living South-Eastern Asia or sub-Saharan Africa but is rare in tumors of patients coming from other regions of the world [7][8][9]. In some occasions, TP53 R249S has even been found in more than half of the tumors investigated.…”

Section: Introductionmentioning

confidence: 99%

Droplet digital PCR detects high rate of TP53 R249S mutants in cell-free DNA of middle African patients with hepatocellular carcinoma

et al. 2018

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Hepatocellular carcinoma (HCC) is still a major killing malignancy in sub-Saharan Africa. Lifelong intoxication with aflatoxin B1 is considered as one of the primary causes of this situation. The role of aflatoxin in HCC from a given population is commonly estimated through the prevalence of R249S mutation of TP53, a hallmark for previous exposure to the mycotoxin. However, the role of AFB1 is barely known in large part of Africa. We conducted a survey on circulating cell-free DNA from 149 patients with HCC and 213 control subjects with and without liver diseases from Cameroon and Central African Republic using droplet digital PCR technique. We observed a mutation prevalence of 24.8% (n = 37/149) in patients with tumor and 5.6% (n = 12/213) in controls (P = 2.2E-07). Patients with mutations usually displayed significantly increased circulating alpha-fetoprotein (AFP) values, high hepatitis B virus (HBV) DNA loads as well as worsened values of blood cells count. Interestingly, the fraction of droplets positive for R249S was significantly larger in patients with liver cancer (15.3 ± 3.7%) than in controls (0.5 ± 0.3%, P = 7.1E-04). Our survey indicates that AFB1 is instrumental for HCC development in Middle Africa and that droplet digital PCR might be used in the region both to diagnose HCC and to conduct public health surveys on populations at risk of chronic aflatoxin intoxication.

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“…6 Second, liver parenchyma exhibited a very low level of in ammatory response and an absence of brotic process, and this, despite a strong prevalence of underlying infection with hepatitis B virus. 7,8 However, we observed within the non-tumor liver (NTL) parenchyma the presence of foci of cellular alteration in which cells are smaller compared to regular hepatocytes and exhibit an altered nuclear-cytoplasmic ratio. 7 These foci of cellular alteration showed also some degree of congruence with the co-expression of precancerous marker glutamine synthetase.…”

Section: Read Full Licensementioning

confidence: 89%

Metallomic Profile in Non-cirrhotic Hepatocellular Carcinoma Supports a Phenomenon of Metal Metabolism Adaptation in Tumor Cells

Cano

Bertani

Island

et al. 2020

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Our group has previously described a particular form of Hepatocellular carcinoma (HCC) developed in non-cirrhotic liver (HCC-NC) developed in Peruvian patients Our aim is to analyze the HCC-NC from clinical-biological findings in two different cohorts (Peruvian and French) and the link with metallomic profile. Clinical, histopathological and also tumoral (T) and non-tumoral liver (NTL) samples of 38 Peruvian and 45 French patients were studied. Twelve metals were assayed using ICP/MS: Mn, Fe, Cu, Co, Zn, As, Se, Rb, Mo, Cd, Pb, and Sn. Possible associations between metals and survival were also evaluated. Overall, results show clearly differences between both cohorts. Mean age were 41 ± 20 and 68 ± 9 years-old for Peruvians and French, respectively. 80% of Peruvian patients were positive for the HBsAg, versus 9% in French patients. Metals concentrations were higher in the NTL of Peruvians (p < 0.05) compared to the French. In both cohort metal concentrations were lower in HCC areas compared to NTL, excepted for Cu for which mean concentration was increased in HCC (p < 0.05). Se concentration in HCC was associated with better survival only in Peruvians. Our data shows, in both HCC-NC cohorts, that the process of hepatic tumorigenesis impact similarity the metallomic profile in tumor.

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Early-onset liver cancer in South America associates with low hepatitis B virus DNA burden

Cited by 31 publications

References 38 publications

Quantitative analysis of the splice variants expressed by the major hepatitis B virus genotypes

Quantitative analysis of the splice variants expressed by the major hepatitis B virus genotypes

Droplet digital PCR detects high rate of TP53 R249S mutants in cell-free DNA of middle African patients with hepatocellular carcinoma

Metallomic Profile in Non-cirrhotic Hepatocellular Carcinoma Supports a Phenomenon of Metal Metabolism Adaptation in Tumor Cells

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