Proteomics Used in Identifying Novel Correlates of Disease in Pediatric Metabolic Dysfunction-Associated Steatotic Liver Disease.
Document Type
Article
Publication Date
6-2025
Identifier
DOI: 10.1111/cts.70271
Abstract
Metabolic dysfunction-associated liver disease (MASLD) is a leading cause of liver disease in children. There is a paucity of data on potential biomarkers and therapeutic targets, especially in pediatric MASLD. We used mass spectrometry (MS)-mediated proteomics followed by enzyme-linked immunosorbent assay (ELISA) to identify potential biomarkers and therapeutic targets in pediatric MASLD. Serum samples were collected from pediatric subjects without (n = 56) and with MASLD (n = 72). Initial screen using MS-based proteomics identified 6 upregulated (adenosine deaminase 2, sex hormone-binding globulin (SHBG), inter-alpha-trypsin inhibitor heavy chain H1 (ITIH1), fructose-bisphosphate aldolase A, type II cytoskeletal 2 epidermal keratine, N-acetylmuramoyl-L-alanine amidase) and 3 downregulated (alcohol dehydrogenase 4 (ADH4), fructose-bisphosphate aldolase B (ALDOB), serum albumin) proteins in the MASLD group. Confirmatory studies using ELISA were performed for the 2 strongest upregulated proteins (SHBG and ITIH1) and two top downregulated proteins (ADH4 and ALDOB). Correlation of ELISA results with clinical data revealed that SHBG had strong associations with BMI, ALT, and HgbA1c (p < 0.05). ADH4 had strong associations with BMI and HgbA1c (p < 0.05). ITIH1 and ALDOB had no strong correlations with common clinical parameters of MASLD. Area under ROC Curve revealed statistically significant ability of SHBG (494 nmol/L, sensitivity = 98%, specificity 80%) and ADH4 (2.14 ng/mL, sensitivity = 65%, specificity = 66%) to diagnosis MASLD (p < 0.05). MS with confirmation ELISA identified SHBG and ADH4 as potential biomarkers of pediatric MASLD.
Journal Title
Clin Transl Sci
Volume
18
Issue
6
First Page
70271
Last Page
70271
MeSH Keywords
Humans; Proteomics; Male; Child; Female; Biomarkers; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Adolescent; Fatty Liver; Infant; ROC Curve; Mass Spectrometry
PubMed ID
40522163
Keywords
childhood; hepatology; metabolic syndrome; obesity; proteome
Recommended Citation
Paine-Cabrera D, Harvey LK, Pritchard MT, et al. Proteomics Used in Identifying Novel Correlates of Disease in Pediatric Metabolic Dysfunction-Associated Steatotic Liver Disease. Clin Transl Sci. 2025;18(6):e70271. doi:10.1111/cts.70271
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Comments
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