On hepatocellular carcinoma in South America and early-age onset of the disease

Pineau, Pascal; Ruíz, Eloy; Deharo, Eric; Bertani, Stéphane

doi:10.1016/j.clinre.2018.10.019

Cited by 17 publications

(17 citation statements)

References 40 publications

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“…Intriguingly, a similar early-age onset of HCC, associated with the same clade of HBV, has also been described in Alaskan Native people, 10,000 km distant from the Andean communities of Peru [12]. This observation has raised the hypothesis of a particular dynamics in liver cancer shared by people with Indigenous American ancestries [8].…”

Section: Introductionmentioning

confidence: 59%

“…Indeed, there is still a scarcity of molecular information available from HCC patients of Africa, Latin America, and Oceania despite distinctive characteristics exhibited by the disease in these regions. For example, a significant fraction of HCC cases in South America manifests with unusual early-age onset [7,8]. That is especially prevalent in the Andean Natives of Peru, in which non-cirrhotic, non-fibrolamellar HCCs develop in young patients with underlying infection by HBV subtype F1b [9,10].…”

Section: Introductionmentioning

confidence: 99%

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Global DNA hypermethylation pattern and unique gene expression signature in liver cancer from patients with Indigenous American ancestry

et al. 2021

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Hepatocellular carcinoma (HCC) usually afflicts individuals in their maturity after a protracted liver disease. Contrasting with this pattern, the age structure of HCC in Andean people displays a bimodal distribution with half of the patients developing HCC in adolescence and early adulthood. To deepen our understanding of the molecular determinants of the disease in this population, we conducted an integrative analysis of gene expression and DNA methylation in HCC developed by 74 Peruvian patients, including 39 adolescents and young adults. While genome-wide hypomethylation is considered as a paradigm in human HCCs, our analysis revealed that Peruvian tumors are associated with a global DNA hypermethylation. Moreover, pathway enrichment analysis of transcriptome data characterized an original combination of signatures. Peruvian HCC forgoes canonical activations of IGF2, Notch, Ras/MAPK, and TGF-β signals to depend instead on Hippo/YAP1, MYC, and Wnt/β-catenin pathways. These signatures delineate a homogeneous subtype of liver tumors at the interface of the proliferative and non-proliferative classes of HCCs. Remarkably, the development of this HCC subtype occurs in patients with one of the four Native American mitochondrial haplogroups A-D. Finally, integrative characterization revealed that Peruvian HCC is apparently controlled by the PRC2 complex that mediates cell reprogramming with massive DNA methylation modulating gene expression and pinpointed retinoid signaling as a potential target for epigenetic therapy.

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Section: Introductionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Global DNA hypermethylation pattern and unique gene expression signature in liver cancer from patients with Indigenous American ancestry

et al. 2021

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“…It has been reported that sgtF1b possess a higher replication capacity and a major fitness compared to sgtF4 [20,21]. In addition, sgtF1b, the most prevalent in acute and HBeAg positive chronic infections in Argentina, has a delayed HBeAg seroconversion in comparison with genotypes/subgenotype A, F4 and D and, most importantly, it has been associated with a more severe course of chronic infection and HCC progression [18,19,22,24].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, individuals infected with sgtF1b seroconvert to anti-HBe later in life than those infected with sgtF4 [18]. Moreover, growing evidence has shown a close association of sgtF1b with a more severe course of chronic infections, and a high correlation to HCC progression exists among Alaska and Peru people [22,23,24,25].…”

Section: Introductionmentioning

confidence: 99%

Hepatitis B Virus X Gene Differentially Modulates Subgenotype F1b and F4 Replication

Elizalde

Speroni

Campos

et al. 2019

Viruses

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Hepatitis B virus (HBV) is classified into ten genotypes and numerous subgenotypes (sgt). In particular, sgt F1b and sgt F4, native of Latin America, have been associated with differences in clinical and virological characteristics. Hepatitis B virus X protein (HBx) is a multifunctional regulatory protein associated with the modulation of viral transcription and replication. In this work, we analyzed the role of the X gene and the encoded X protein in sgtF1b and sgtF4 replication. Transfection with HBx deficient genomes revealed remarkable differences in the replicative capacity of sgtF1b and sgtF4 mutants. The silencing of HBx increased sgtF1b X(-) transcription and replication by more than 2.5 fold compared to the wild type variant, while it decreased sgtF4 X(-) transcription and replication by more than 3 fold. Trans-complementation of HBx restore sgtF1b and sgtF4 wild type transcription and replication levels. In addition, transfection with chimeric variants, carrying wild type (F1b/XF4 and F4/XF1b) or mutated (F1b/X(-)F4 and F4/X(-)F1b) X gene of one sgt in the backbone of the other sgt, showed that the nucleotide sequence of the X gene, that includes regulatory elements that modulate pgRNA transcription, was responsible for the disparity observed between sgtF1b X(-) and sgtF4 X(-). These results showed that sgtF1b and sgtF4 X gene play a central role in regulating HBV transcription and replication, which eventually lead to a common purpose, to reach wild type replication levels of sgtF1b and sgtF4 viruses.

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“…Altogether, these ndings suggest that the clinical epidemiological situation encountered therein is due to some biological features intrinsic to the natural history of HCC in the population of Peru, and more broadly in South America. 9 This observation prompted us to search for additional pathophysiological cofactors associated with HCC-NC that could enhance the risk of developing at an early age among the Peruvian population.…”

Section: Read Full Licensementioning

confidence: 99%

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

Cano

Bertani

Island

et al. 2020

Preprint

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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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On hepatocellular carcinoma in South America and early-age onset of the disease

Cited by 17 publications

References 40 publications

Global DNA hypermethylation pattern and unique gene expression signature in liver cancer from patients with Indigenous American ancestry

Global DNA hypermethylation pattern and unique gene expression signature in liver cancer from patients with Indigenous American ancestry

Hepatitis B Virus X Gene Differentially Modulates Subgenotype F1b and F4 Replication

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

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