Proteomics Used in Identifying Novel Correlates of Disease in Pediatric Metabolic Dysfunction‐Associated Steatotic Liver Disease
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 imm...
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Wiley
2025-06-01
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| Series: | Clinical and Translational Science |
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| Online Access: | https://doi.org/10.1111/cts.70271 |
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| author | Diego Paine‐Cabrera Lisa K. Harvey Michele T. Pritchard John Thyfault Antonio Artigues Udayan Apte Voytek Slowik |
| author_facet | Diego Paine‐Cabrera Lisa K. Harvey Michele T. Pritchard John Thyfault Antonio Artigues Udayan Apte Voytek Slowik |
| author_sort | Diego Paine‐Cabrera |
| collection | DOAJ |
| description | 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. |
| format | Article |
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| institution | OA Journals |
| issn | 1752-8054 1752-8062 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
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| series | Clinical and Translational Science |
| spelling | doaj-art-05c84aa381674add8f0882e8d5a72b1b2025-08-20T02:22:10ZengWileyClinical and Translational Science1752-80541752-80622025-06-01186n/an/a10.1111/cts.70271Proteomics Used in Identifying Novel Correlates of Disease in Pediatric Metabolic Dysfunction‐Associated Steatotic Liver DiseaseDiego Paine‐Cabrera0Lisa K. Harvey1Michele T. Pritchard2John Thyfault3Antonio Artigues4Udayan Apte5Voytek Slowik6Department of Pharmacology Toxicology and Therapeutics, University of Kansas Medical Center Kansas City Kansas USADivision of Gastroenterology Hepatology, and Nutrition, Children's Mercy—Kansas City Kansas City Missouri USADepartment of Pharmacology Toxicology and Therapeutics, University of Kansas Medical Center Kansas City Kansas USADepartment of Molecular and Integrative Physiology University of Kansas Medical Center Kansas City Kansas USADepartment of Biochemistry and Molecular Biology University of Kansas Medical Center Kansas City Kansas USADepartment of Pharmacology Toxicology and Therapeutics, University of Kansas Medical Center Kansas City Kansas USADivision of Gastroenterology Hepatology, and Nutrition, Children's Mercy—Kansas City Kansas City Missouri USAABSTRACT 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.https://doi.org/10.1111/cts.70271childhoodhepatologymetabolic syndromeobesityproteome |
| spellingShingle | Diego Paine‐Cabrera Lisa K. Harvey Michele T. Pritchard John Thyfault Antonio Artigues Udayan Apte Voytek Slowik Proteomics Used in Identifying Novel Correlates of Disease in Pediatric Metabolic Dysfunction‐Associated Steatotic Liver Disease Clinical and Translational Science childhood hepatology metabolic syndrome obesity proteome |
| title | Proteomics Used in Identifying Novel Correlates of Disease in Pediatric Metabolic Dysfunction‐Associated Steatotic Liver Disease |
| title_full | Proteomics Used in Identifying Novel Correlates of Disease in Pediatric Metabolic Dysfunction‐Associated Steatotic Liver Disease |
| title_fullStr | Proteomics Used in Identifying Novel Correlates of Disease in Pediatric Metabolic Dysfunction‐Associated Steatotic Liver Disease |
| title_full_unstemmed | Proteomics Used in Identifying Novel Correlates of Disease in Pediatric Metabolic Dysfunction‐Associated Steatotic Liver Disease |
| title_short | Proteomics Used in Identifying Novel Correlates of Disease in Pediatric Metabolic Dysfunction‐Associated Steatotic Liver Disease |
| title_sort | proteomics used in identifying novel correlates of disease in pediatric metabolic dysfunction associated steatotic liver disease |
| topic | childhood hepatology metabolic syndrome obesity proteome |
| url | https://doi.org/10.1111/cts.70271 |
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