Dataset Information

Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) affects 25% of the population and can progress to cirrhosis, where treatment options are limited. As the liver secrets most of the blood plasma proteins its diseases should affect the plasma proteome. Plasma proteome profiling on 48 patients with cirrhosis or NAFLD with normal glucose tolerance or diabetes, revealed 8 significantly changing (ALDOB, APOM, LGALS3BP, PIGR, VTN, IGHD, FCGBP and AFM), two of which are already linked to liver disease. Polymeric immunoglobulin receptor (PIGR) was significantly elevated in both cohorts with a 2.7-fold expression change in NAFLD and 4-fold change in cirrhosis and was further validated in mouse models. Furthermore, a global correlation map of clinical and proteomic data strongly associated DPP4, ANPEP, TGFBI, PIGR, and APOE to NAFLD and cirrhosis. DPP4 is a known drug target in diabetes. ANPEP and TGFBI are of interest because of their potential role in extracellular matrix remodeling in fibrosis.

OTHER RELATED OMICS DATASETS IN: PXD012056PXD011839

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Matthias Mann

PROVIDER: MSV000084333 | MassIVE |

SECONDARY ACCESSION(S): PXD011839

REPOSITORIES: MassIVE

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Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease.

Niu Lili L Geyer Philipp E PE Wewer Albrechtsen Nicolai J NJ Gluud Lise L LL Santos Alberto A Doll Sophia S Treit Peter V PV Holst Jens J JJ Knop Filip K FK Vilsbøll Tina T Junker Anders A Sachs Stephan S Stemmer Kerstin K Müller Timo D TD Tschöp Matthias H MH Hofmann Susanna M SM Mann Matthias M

Molecular systems biology 20190301 3

Non-alcoholic fatty liver disease (NAFLD) affects 25% of the population and can progress to cirrhosis with limited treatment options. As the liver secretes most of the blood plasma proteins, liver disease may affect the plasma proteome. Plasma proteome profiling of 48 patients with and without cirrhosis or NAFLD revealed six statistically significantly changing proteins (ALDOB, APOM, LGALS3BP, PIGR, VTN, and AFM), two of which are already linked to liver disease. Polymeric immunoglobulin recepto ...[more]

PMID: 30824564

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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.

Dataset Information

Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease

Publications

Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease.

Similar Datasets

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