Plasma cell-free DNA methylation: a liquid biomarker of hepatic fibrosis

Yigit, Buket; Boyle, Marie; Özler, Oğuz; Erden, Nihan; Tutucu, Faik; Hardy, Timothy; Bergmann, Christina; Distler, J.; Adali, Güpse; Dayangaç, Murat; Mann, Derek A.; Zeybel, Müjdat; Mann, Jelena

doi:10.1136/gutjnl-2017-315668

Cited by 22 publications

(17 citation statements)

References 2 publications

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“…Considerable efforts have been dedicated to the use cfDNA for the prediction of liver fibrosis associated with NASH and alcoholic liver disease[ 31 ]; however, the preliminary results indicate substantial lack of specificity, as they can be completely unrelated to NASH-biology[ 32 ]. Furthermore, the fact that cfDNA circulates not only at very low concentrations but is also highly fragmented imposes analytical and technical challenges that are very difficult to overcome[ 33 ].…”

Section: Cell-free Dna and Rna As Noninvasive Biomarkers Of Nashmentioning

confidence: 99%

Multiomics biomarkers for the prediction of nonalcoholic fatty liver disease severity

Pirola¹,

Sookoian²

2018

WJG

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This review intends to uncover how information from large-scale genetic profiling (whole genome sequencing, and whole exome sequencing) of nonalcoholic fatty liver disease (NAFLD), as well as information from circulating transcriptomics (cell-free miRNAs) and metabolomics, contributes to the understanding of NAFLD pathogenesis. A further aim is to address the question of whether OMICs information is ready to be implemented in the clinics. The available evidence suggests that any new knowledge pertaining to molecular signatures associated with NAFLD and nonalcoholic steatohepatitis should be promptly translated into the clinical setting. Nevertheless, rigorous steps that must include validation and replication are mandatory before utilizing OMICs biomarkers in diagnostics to identify patients at risk of advanced disease, including liver cancer.

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Section: Cell-free Dna and Rna As Noninvasive Biomarkers Of Nashmentioning

confidence: 99%

Multiomics biomarkers for the prediction of nonalcoholic fatty liver disease severity

Pirola¹,

Sookoian²

2018

WJG

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“…Steadily accumulating clinical information has suggested that the DNA methylation of key genes contributes to the pathobiology of NAFLD by silencing or activating genes via hypermethylation or hypomethylation, respectively . For example, the DNA methylation levels of antifibrogenic genes (peroxisome proliferator activated receptor [ PPAR ] α , γ , and δ ) in the liver were found to increase with hepatic fibrosis severity in patients with NAFLD and alcoholic fatty liver disease . Moreover, in participants with advanced NAFLD, many tissue repair genes, such as fibroblast growth factor receptor 2 ( FGFR 2) and caspase 1 ( CASP 1 ), were hypomethylated .…”

Section: Introductionmentioning

confidence: 99%

Association of Hepatic Global DNA Methylation and Serum One‐Carbon Metabolites with Histological Severity in Patients with NAFLD

Lai

Chen

Ding

et al. 2019

Obesity

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Objective Clinical relevance of global DNA methylation and one‐carbon metabolite levels with histological severity remains uncertain in patients with nonalcoholic fatty liver disease (NAFLD). This study aimed to evaluate hepatic global DNA methylation and serum one‐carbon metabolite concentrations in patients with NAFLD and the possible associations of these parameters with liver histology. Methods Liver biopsies from 18 control participants and 47 patients with NAFLD were evaluated. Results The hepatic global DNA methylation level was significantly lower in the NAFLD group than in the control group among participants with overweight. Participants with moderate inflammation and mild fibrosis had significantly lower levels of global DNA methylation than those without these characteristics. Participants with borderline nonalcoholic steatohepatitis had significantly lower global DNA methylation levels than controls. The hepatic global DNA methylation level tended to decrease with the increasing hepatic inflammation grade and disease progression. The NAFLD group had a significantly higher serum homocysteine concentration than the control group among participants with overweight. This level tended to increase with increasing hepatic steatosis grade and disease progression. Conclusions Patients with NAFLD exhibited lower hepatic levels of global DNA methylation and elevated serum homocysteine concentrations, which are associated with the histological severity of NAFLD.

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“…In addition, a test based on plasma DNA methylation at the PPARγ gene promoter outperforms the commonly used NAFLD fibrosis score. A follow-up study confirmed that high CpG methylation at PPARγ promoter is associated with severe fibrosis/cirrhosis in NAFLD and in HBV, suggesting that this phenomenon is not limited to metabolic liver diseases 28. Furthermore, this methylation signature remains unaffected by the presence of HCC.…”

Section: Circulating Nucleic Acidsmentioning

confidence: 76%

“…Furthermore, this methylation signature remains unaffected by the presence of HCC. Intriguingly, the signature appears to be specific to hepatic fibrosis as patients with diffuse systemic sclerosis, where a number of organs are affected by severe fibrosis, but not the liver itself, have very low level of DNA methylation at the PPARγ promoter 28…”

Section: Circulating Nucleic Acidsmentioning

confidence: 99%

Liquid biopsy for liver diseases

Mann

Reeves

Feldstein

2018

Gut

Self Cite

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With the growing number of novel therapeutic approaches for liver diseases, significant research efforts have been devoted to the development of liquid biopsy tools for precision medicine. This can be defined as non-invasive reliable biomarkers that can supplement and eventually replace the invasive liver biopsy for diagnosis, disease stratification and monitoring of response to therapeutic interventions. Similarly, detection of liver cancer at an earlier stage of the disease, potentially susceptible to curative resection, can be critical to improve patient survival. Circulating extracellular vesicles, nucleic acids (DNA and RNA) and tumour cells have emerged as attractive liquid biopsy candidates because they fulfil many of the key characteristics of an ideal biomarker. In this review, we summarise the currently available information regarding these promising and potential transformative tools, as well as the issues still needed to be addressed for adopting various liquid biopsy approaches into clinical practice. These studies may pave the way to the development of a new generation of reliable, mechanism-based disease biomarkers.

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Plasma cell-free DNA methylation: a liquid biomarker of hepatic fibrosis

Cited by 22 publications

References 2 publications

Multiomics biomarkers for the prediction of nonalcoholic fatty liver disease severity

Multiomics biomarkers for the prediction of nonalcoholic fatty liver disease severity

Association of Hepatic Global DNA Methylation and Serum One‐Carbon Metabolites with Histological Severity in Patients with NAFLD

Liquid biopsy for liver diseases

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