Dataset Information

Plasma ALS and LG3BP predict liver fibrosis in NAFLD patients

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is estimated to affect 25% of the world’s population and its prevalence is increasing with the rise in obesity. The evolution of this disease includes different pathological stages: steatosis, inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Liver biopsy stands as the gold standard for NAFLD assessment despite its invasive nature and limited performance. Liver fibrosis is the most important clinical parameter, as it is closely related to mortality, and biopsies are only considered when advanced fibrosis is suspected. This scenario makes the finding of a non-invasive and reliable biomarker an urgent need for an accurate diagnosis. To this end, we first performed a discovery study on 159 plasma samples from histologically characterised NAFLD patients using mass spectrometry (MS)-based quantitative proteomics. Insulin-like growth factor-binding protein complex acid labile (ALS, P35858) and Galectin-3-binding protein (LG3BP, Q08380) were selected for a verification by enzyme-linked immunosorbent assay (ELISA) in the same cohort and finally validated in an independent NAFLD cohort of 200 plasma samples.ALS and LG3BP were validated as advanced liver fibrosis biomarkers and successfully included in a panel with FibroTest variables. ELISA kits availability would allow to achieve relatively fast clinical translation if further investigations in larger cohorts confirm these results.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Non-alcoholic Fatty Liver Disease

SUBMITTER: Hesse Anne-Marie

LAB HEAD: Yohann Couté

PROVIDER: PXD043340 | Pride | 2024-05-22

REPOSITORIES: Pride

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Plasma ALS and Gal-3BP differentiate early from advanced liver fibrosis in MASLD patients.

Pérez Compte David D Etourneau Lucas L Hesse Anne-Marie AM Kraut Alexandra A Barthelon Justine J Sturm Nathalie N Borges Hélène H Biennier Salomé S Courçon Marie M de Saint Loup Marc M Mignot Victoria V Costentin Charlotte C Burger Thomas T Couté Yohann Y Bruley Christophe C Decaens Thomas T Jaquinod Michel M Boursier Jérôme J Brun Virginie V

Biomarker research 20240429 1

<h4>Background</h4>Metabolic dysfunction-associated steatotic liver disease (MASLD) is estimated to affect 30% of the world's population, and its prevalence is increasing in line with obesity. Liver fibrosis is closely related to mortality, making it the most important clinical parameter for MASLD. It is currently assessed by liver biopsy - an invasive procedure that has some limitations. There is thus an urgent need for a reliable non-invasive means to diagnose earlier MASLD stages.<h4>Methods< ...[more]

PMID: 38679739

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Project description:Background & Aims: Cirrhosis and liver cancer are potential outcomes of advanced nonalcoholic fatty liver disease (NAFLD). It is not clear what factors determine whether patients will develop advanced or mild NAFLD, limiting non-invasive diagnosis and treatment before clinical sequelae emerge. We investigated whether DNA methylation profiles can distinguish patients with mild disease from those with advanced NAFLD, and how these patterns are functionally related to hepatic gene expression. Methods: We collected frozen liver biopsies and clinical data from patients with biopsy-proven NAFLD (56 in the discovery cohort and 34 in the replication cohort). Samples were divided into groups based on histologic severity of fibrosis: F0?1 (mild) and F3?4 (advanced). DNA methylation profiles were determined and coupled with gene expression data from the same biopsies; differential methylation was validated in subsets of the discovery and replication cohorts. We then analyzed interactions between the methylome and transcriptome. Results: Clinical features did not differ between patients known to have mild or advanced fibrosis based on biopsy analysis. There were 69,247 differentially methylated CpG sites (76% hypomethylated, 24% hypermethylated) in patients with advanced vs mild NAFLD (P<.05). Methylation at FGFR2, MAT1A, and CASP1 was validated by bisulfite pyrosequencing and the findings were reproduced in the replication cohort. Methylation correlated with gene transcript levels for 7% of differentially methylated CpG sites, indicating that differential methylation contributes to differences in expression. In samples with advanced NAFLD, many tissue repair genes were hypomethylated and overexpressed, whereas genes in certain metabolic pathways, including 1-carbon metabolism, were hypermethylated and under-expressed. Conclusions: Functionally relevant differences in methylation can distinguish patients with advanced vs mild NAFLD. Altered methylation of genes that regulate processes such as steatohepatitis, fibrosis, and carcinogenesis indicate the role of DNA methylation in progression of NAFLD. Three technical replicates were included for quality control along with 35 mild NAFLD (33 unique samples) and 24 advanced NAFLD (23 unique sample). One sample per technical duplication was randomly included for a total of 56 NAFLD samples used for study.

			Action	DRS
	HF2_010887.mgf	Mgf
	HF2_010887.raw	Raw
	HF2_010890.mgf	Mgf
	HF2_010890.raw	Raw
	HF2_010893.mgf	Mgf