Validating candidate biomarkers for different stages of non-alcoholic fatty liver disease

Al-Qarni, Reem; Iqbal, Muhammad Darwesh; Alotaibi, Maram; Alsaif, Faisal; Alfadda, Assim A.; Alkhalidi, Hisham; Bamehriz, Fahad; Hassanain, Mazen

doi:10.1097/md.0000000000021463

Cited by 5 publications

(6 citation statements)

References 58 publications

(50 reference statements)

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“…In conclusion, the histological characteristics (significant fibrosis), enrichment analysis, and immune cell infiltration results (marked infiltration of M1 macrophages and CD8 T cells) all indicated that molecular subtype I was associated with significant fibrosis, and thus, molecular subtype I was named fibrotic NAFLD. Further, collagen type I alpha 1 chain (COL1A1) ( 14 ) and thrombospondin 2 (TSP2) ( 15 ) exhibited the highest expression levels in molecular subtype I as biomarkers of the advanced fibrosis stage of NAFLD ( Figures 8A, B ) , demonstrating that molecular subtype I had the most significant fibrosis. The treatment of molecular subtype I NAFLD should focus on decreasing liver collagen deposition and increasing fibrinolysis.…”

Section: Discussionmentioning

confidence: 99%

“…type I alpha 1 chain (COL1A1)(14) and thrombospondin 2 (TSP2) (15) exhibited the highest expression levels in molecular subtype I as biomarkers of the advanced fibrosis stage of NAFLD (Figures8A, B), demonstrating that molecular subtype I had the most significant fibrosis. The treatment of molecular subtype I NAFLD should focus on decreasing liver collagen deposition and increasing fibrinolysis.…”

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confidence: 99%

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Identification of the Non-Alcoholic Fatty Liver Disease Molecular Subtypes Associated With Clinical and Immunological Features via Bioinformatics Methods

Liu

2022

Front. Immunol.

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BackgroundNon-alcoholic fatty liver disease (NAFLD) is a manifestation of metabolic syndrome in the liver with varying severity. Heterogeneity in terms of molecules and immune cell infiltration drives NAFLD from one stage to the next. However, a precise molecular classification of NAFLD is still lacking, and the effects of complex clinical phenotypes on the efficacy of drugs are usually ignored.MethodsWe introduced multiple omics data to differentiate NAFLD subtypes via consensus clustering, and a weighted gene co-expression network analysis was used to identify eight co-expression modules. Further, eigengenes of eight modules were analyzed with regard to Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways. Furthermore, the infiltration rates of 22 immune cell types were calculated with CIBERSORT and the ESTIMATE algorithm.ResultsIn total, 111 NAFLD patients from three independent GEO datasets were divided into four molecular subtypes, and the corresponding clinical features and immune cell infiltration traits were determined. Based on high gene expression correlations, four molecular subtypes were further divided into eight co-expression modules. We also demonstrated a significant correlation between gene modules and clinical phenotypes. Moreover, we integrated phenotypic, immunologic, and genetic data to assess the potential for progression of different molecular subtypes. Furthermore, the efficacy of drugs against various NAFLD molecular subtypes was discussed to aid in individualized therapy.ConclusionOverall, this study could provide new insights into the underlying pathogenesis of and drug targets for NAFLD.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Identification of the Non-Alcoholic Fatty Liver Disease Molecular Subtypes Associated With Clinical and Immunological Features via Bioinformatics Methods

Liu

2022

Front. Immunol.

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“…Захисний ефект генотипу AA SNV rs4374383 пов'язаний з низькою експресією гена MerTK у печінці. Клінічно значущий фіброз (стадії F2-F4) спостерігається у 19 % хворих з генотипом AA порівняно з 30 % хворих з генотипами GG або GA SNV rs4374383 (ВР = 0,43; 95% ДІ: 0,21-0,88) гена MerTK [125][126][127][128].…”

Section: генетичні фактори що впливають на розвиток метаболічно асоці...unclassified

Genetic predisposition to metabolic dysfunction-associated fatty liver disease

Abaturov,

Nikulina

2024

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The literature review highlights the issue of genetic risk factors associated with the development of metabolic dysfunction-associated fatty liver disease. Human genetic examinations revealed 132 genes among which 32 loci are strongly associated with the pathogenesis of metabolic dysfunction-associated fatty liver disease. It has been found that the risk of developing metabolic dysfunction-associated fatty liver disease is carried by single-nucleotide variants of various genes whose products are involved in lipid and carbohydrate metabolism, maintenance of the redox state, the development of inflammation and fibrosis of liver tissue, which are components of metabolic dysfunction-associated fatty liver disease reactome. The authors presented a detailed list of genetic factors singling out those that influence the risk of metabolic dysfunction-associated fatty liver disease and directly metabolic dysfunction-associated steatohepatitis and liver fibrosis. Also, they emphasized that it is the single-nucleotide variants of the genes of protein 3 containing a patatin-like phospholipase domain, transmembrane 6 superfamily member 2, and 17b-hydroxysteroid dehydrogenase type 13 that are characterized by the highest degree of association with metabolic dysfunction-associated fatty liver disease (odds ratio > 1.6) compared to single-nucleotide variants of other genes identified by gene association studies. The combination of several polymorphisms increases the risk of development and severity of metabolic dysfunction-associated fatty liver disease. The additive steatogenic effect of protein 3 single-nucleotide gene variants containing a patatin-like phospholipase domain and transmembrane 6 superfamily member 2 is probably due to an increased expression of genes involved in de novo lipogenesis. The authors emphasize the need for genetic risk assessment of metabolic dysfunction-associated fatty liver disease, which should include molecular genetic testing at an early stage of examination.

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“…Thus, a topical issue on the agenda is the search for new biomarkers of NAFLD progression. A suggestion regarding biochemical markers, e.g., using the content of some proteins in plasma, namely, PNPLA3 and PPP1R3B as biomarkers of steatosis and COL1A1 as a potential marker of fibrosis in NAFLD [19], is useful. Studies have argued that single biomarkers are hardly diagnostic or predictive of disease stages because of their heterogeneity [20].…”

Section: Approaches For Assessing Nafld Progressionmentioning

confidence: 99%

“…A previous study demonstrated that the activation of an axis, m 6 A-catalytic enzyme methyltransferase-like 3 [(METTL3)/ REVIEW Genes & cells Vol. 19 (1) 2024 metastasis-associated lung adenocarcinoma transcript 1 (MALAT1; a lncRNA)/polypyrimidine tract-binding protein 1 (PTBP1; an RNA-binding protein)/ubiquitin-specific peptidase 8 (USP8; a deubiquitinating enzyme)/transforming growth factor β-activated kinase 1 (TAK1, a kinase)], may promote pyroptosis and M1 polarization of hepatic macrophages [120]. Neutrophils and macrophages may also release exosomes that subsequently modify liver function.…”

Section: Macrophagesmentioning

confidence: 99%

Immune cell balance as potential biomarker of progressing non-alcoholic fatty liver disease

Topchieva,

Kurbatova,

Dudanova

et al. 2024

Genes & Cells

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Non-alcoholic fatty liver disease (NAFLD) is a widespread chronic, slowly progressive metabolic multifactorial disease. It is represented by a number of clinical and morphological forms: steatosis, non-alcoholic steatohepatitis (NASH) (with or without fibrosis) and liver cirrhosis. The search for minimally invasive and cost-effective biomarkers of NAFLD is a key task in the diagnosis, staging of progression, and long-term monitoring of NAFLD. The article discusses the possibility of using the balance of immune cells as potential minimally invasive peripheral markers of NAFLD progression. In the progression of NASH (from steatosis to fibrosis and cirrhosis) an important role is played by inflammation realized due to the activation Kupffer cells, and increased migration of monocytes, dendritic cells, neutrophils, activated T-lymphocytes into the tissues of the organ. Macrophages originating from monocytes, with the progression of NASH, gradually begin to prevail over the pool of resident macrophages. The risk of developing NASH and fibrosis in patients with NAFLD increases with the ratio of neutrophils/lymphocytes in the liver. An increase in the number of Th17 and decrease in Treg cells can contribute to increased hepatic steatosis and the development of inflammation in NAFLD, as well as accelerate the transition from simple steatosis to steatohepatitis and fibrosis.

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Validating candidate biomarkers for different stages of non-alcoholic fatty liver disease

Cited by 5 publications

References 58 publications

Identification of the Non-Alcoholic Fatty Liver Disease Molecular Subtypes Associated With Clinical and Immunological Features via Bioinformatics Methods

Identification of the Non-Alcoholic Fatty Liver Disease Molecular Subtypes Associated With Clinical and Immunological Features via Bioinformatics Methods

Genetic predisposition to metabolic dysfunction-associated fatty liver disease

Immune cell balance as potential biomarker of progressing non-alcoholic fatty liver disease

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