Urine Proteome in Distinguishing Hepatic Steatosis in Patients with Metabolic-Associated Fatty Liver Disease
Background: In patients with metabolic-associated fatty liver disease (MAFLD), hepatic steatosis is the first step of diagnosis, and it is a risk predictor that independently predicts insulin resistance, cardiovascular risk, and mortality. Urine biomarkers have the advantage of being less complex, w...
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MDPI AG
2022-06-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/12/6/1412 |
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| author | Chang-Hai Liu Shanshan Zheng Shisheng Wang Dongbo Wu Wei Jiang Qingmin Zeng Yi Wei Yong Zhang Hong Tang |
| author_facet | Chang-Hai Liu Shanshan Zheng Shisheng Wang Dongbo Wu Wei Jiang Qingmin Zeng Yi Wei Yong Zhang Hong Tang |
| author_sort | Chang-Hai Liu |
| collection | DOAJ |
| description | Background: In patients with metabolic-associated fatty liver disease (MAFLD), hepatic steatosis is the first step of diagnosis, and it is a risk predictor that independently predicts insulin resistance, cardiovascular risk, and mortality. Urine biomarkers have the advantage of being less complex, with a lower dynamic range and fewer technical challenges, in comparison to blood biomarkers. Methods: Hepatic steatosis was measured by magnetic resonance imaging (MRI), which measured the proton density fat fraction (MRI-PDFF). Mild hepatic steatosis was defined as MRI-PDFF 5–10% and severe hepatic steatosis was defined as MRI-PDFF > 10%. Results: MAFLD patients with any kidney diseases were excluded. There were 53 proteins identified by mass spectrometry with significantly different expressions among the healthy control, mild steatosis, and severe steatosis patients. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of these significantly changed urinary molecular features correlated with the liver, resulting in the dysregulation of carbohydrate derivative/catabolic/glycosaminoglycan/metabolic processes, insulin-like growth factor receptor levels, inflammatory responses, the PI3K–Akt signaling pathway, and cholesterol metabolism. Urine alpha-1-acid glycoprotein 1 (ORM1) and ceruloplasmin showed the most significant correlation with the clinical parameters of MAFLD status, including liver fat content, fibrosis, ALT, triglycerides, glucose, HOMA-IR, and C-reactive protein. According to ELISA and western blot (30 urine samples, normalized to urine creatinine), ceruloplasmin (ROC 0.78, <i>p</i> = 0.034) and ORM1 (ROC 0.87, <i>p</i> = 0.005) showed moderate diagnostic accuracy in distinguishing mild steatosis from healthy controls. Ceruloplasmin (ROC 0.79, <i>p</i> = 0.028) and ORM1 (ROC 0.81, <i>p</i> = 0.019) also showed moderate diagnostic accuracy in distinguishing severe steatosis from mild steatosis. Conclusions: Ceruloplasmin and ORM1 are potential biomarkers in distinguishing mild and severe steatosis in MAFLD patients. |
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| language | English |
| last_indexed | 2024-03-10T00:00:02Z |
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| spelling | doaj.art-180dc619a0434d69894b2984a51cc32d2023-11-23T16:17:43ZengMDPI AGDiagnostics2075-44182022-06-01126141210.3390/diagnostics12061412Urine Proteome in Distinguishing Hepatic Steatosis in Patients with Metabolic-Associated Fatty Liver DiseaseChang-Hai Liu0Shanshan Zheng1Shisheng Wang2Dongbo Wu3Wei Jiang4Qingmin Zeng5Yi Wei6Yong Zhang7Hong Tang8Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Transplant Engineering and Immunology, MOH, West China-Washington Mitochondria and Metabolism Research Center, West China Hospital, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Transplant Engineering and Immunology, MOH, West China-Washington Mitochondria and Metabolism Research Center, West China Hospital, Sichuan University, Chengdu 610041, ChinaCenter of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, ChinaCenter of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, ChinaCenter of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, ChinaDepartment of Radiology, West China Hospital, Sichuan University, Chengdu 610041, ChinaInstitutes for Systems Genetics, West China Hospital, Sichuan University, Chengdu 610041, ChinaCenter of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, ChinaBackground: In patients with metabolic-associated fatty liver disease (MAFLD), hepatic steatosis is the first step of diagnosis, and it is a risk predictor that independently predicts insulin resistance, cardiovascular risk, and mortality. Urine biomarkers have the advantage of being less complex, with a lower dynamic range and fewer technical challenges, in comparison to blood biomarkers. Methods: Hepatic steatosis was measured by magnetic resonance imaging (MRI), which measured the proton density fat fraction (MRI-PDFF). Mild hepatic steatosis was defined as MRI-PDFF 5–10% and severe hepatic steatosis was defined as MRI-PDFF > 10%. Results: MAFLD patients with any kidney diseases were excluded. There were 53 proteins identified by mass spectrometry with significantly different expressions among the healthy control, mild steatosis, and severe steatosis patients. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of these significantly changed urinary molecular features correlated with the liver, resulting in the dysregulation of carbohydrate derivative/catabolic/glycosaminoglycan/metabolic processes, insulin-like growth factor receptor levels, inflammatory responses, the PI3K–Akt signaling pathway, and cholesterol metabolism. Urine alpha-1-acid glycoprotein 1 (ORM1) and ceruloplasmin showed the most significant correlation with the clinical parameters of MAFLD status, including liver fat content, fibrosis, ALT, triglycerides, glucose, HOMA-IR, and C-reactive protein. According to ELISA and western blot (30 urine samples, normalized to urine creatinine), ceruloplasmin (ROC 0.78, <i>p</i> = 0.034) and ORM1 (ROC 0.87, <i>p</i> = 0.005) showed moderate diagnostic accuracy in distinguishing mild steatosis from healthy controls. Ceruloplasmin (ROC 0.79, <i>p</i> = 0.028) and ORM1 (ROC 0.81, <i>p</i> = 0.019) also showed moderate diagnostic accuracy in distinguishing severe steatosis from mild steatosis. Conclusions: Ceruloplasmin and ORM1 are potential biomarkers in distinguishing mild and severe steatosis in MAFLD patients.https://www.mdpi.com/2075-4418/12/6/1412metabolic-associated fatty liver diseaseproteomicshepatic steatosis |
| spellingShingle | Chang-Hai Liu Shanshan Zheng Shisheng Wang Dongbo Wu Wei Jiang Qingmin Zeng Yi Wei Yong Zhang Hong Tang Urine Proteome in Distinguishing Hepatic Steatosis in Patients with Metabolic-Associated Fatty Liver Disease Diagnostics metabolic-associated fatty liver disease proteomics hepatic steatosis |
| title | Urine Proteome in Distinguishing Hepatic Steatosis in Patients with Metabolic-Associated Fatty Liver Disease |
| title_full | Urine Proteome in Distinguishing Hepatic Steatosis in Patients with Metabolic-Associated Fatty Liver Disease |
| title_fullStr | Urine Proteome in Distinguishing Hepatic Steatosis in Patients with Metabolic-Associated Fatty Liver Disease |
| title_full_unstemmed | Urine Proteome in Distinguishing Hepatic Steatosis in Patients with Metabolic-Associated Fatty Liver Disease |
| title_short | Urine Proteome in Distinguishing Hepatic Steatosis in Patients with Metabolic-Associated Fatty Liver Disease |
| title_sort | urine proteome in distinguishing hepatic steatosis in patients with metabolic associated fatty liver disease |
| topic | metabolic-associated fatty liver disease proteomics hepatic steatosis |
| url | https://www.mdpi.com/2075-4418/12/6/1412 |
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