Identification of tryptophan metabolism-related biomarkers for nonalcoholic fatty liver disease through network analysis
Background: Increasing evidence demonstrates that tryptophan metabolism is closely related to the development of nonalcoholic fatty liver disease (NAFLD). This study aimed to identify specific biomarkers of NAFLD associated with tryptophan metabolism and research its functional mechanism. Methods: W...
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Bioscientifica
2025-04-01
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| Series: | Endocrine Connections |
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| Online Access: | https://ec.bioscientifica.com/view/journals/ec/14/5/EC-24-0470.xml |
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| author | Cuihua Jiang Jianqi Liang Kaibo Hu Yanqing Ye Jiajia Yang Xiaozhi Zhang Guilin Ye Jing Zhang Deju Zhang Bin Zhong Peng Yu Liefeng Wang Bin Zeng |
| author_facet | Cuihua Jiang Jianqi Liang Kaibo Hu Yanqing Ye Jiajia Yang Xiaozhi Zhang Guilin Ye Jing Zhang Deju Zhang Bin Zhong Peng Yu Liefeng Wang Bin Zeng |
| author_sort | Cuihua Jiang |
| collection | DOAJ |
| description | Background: Increasing evidence demonstrates that tryptophan metabolism is closely related to the development of nonalcoholic fatty liver disease (NAFLD). This study aimed to identify specific biomarkers of NAFLD associated with tryptophan metabolism and research its functional mechanism. Methods: We downloaded NAFLD RNA-sequencing data from GSE89632 and GSE24807, and obtained tryptophan metabolism-related genes (TMRGs) from the MsigDB database. The R package limma and WGCNA were used to identify TMRGs–DEGs, and GO, KEGG and Cytoscape were used to analyze and visualize the data. Immune cell infiltration analysis was used to explore the immune mechanism of NAFLD and the biomarkers. We also validated extended levels of biomarkers. Results: We identified 375 NAFLD differentially expressed genes (DEGs) and 85 TMRGs–DEGs. GO/KEGG analysis revealed that TMRGs–DEGs were mainly enriched in triglyceride and cholesterol metabolism. ROC curves identified CCL20 (AUC = 0.917), CD160 (AUC = 0.933) and CYP7A1 (AUC = 1) as biomarkers of NAFLD. Immune infiltration analysis showed significant differences in ten immune cells, and the activation of dendritic cells and mast cells were highly positively correlated with NAFLD. CCL20, CD160 and CYP7A1 were highly correlated with M2 macrophage, neutrophil and mast cells activation, respectively. Twenty-seven TMRGs correlated with hub genes, and gene set enrichment analysis demonstrated their function in tryptophan- and lysine-containing metabolic process. We identified 41 therapeutic drug matches which corresponded to two hub genes and four drugs which co-targeted CCL20 and CYP7A1. Finally, three hub genes were validated in our mouse model. Conclusions: CCL20, CD160 and CYP7A1 are tryptophan metabolism-related biomarkers of NAFLD, related to glycerol ester and cholesterol metabolism. We screened four compounds which co-target CCL29 and CYP7A1 to provide potential experimental drugs for NAFLD. |
| format | Article |
| id | doaj-art-9bcd4e26b4f04147ba4d0cc7aa629498 |
| institution | OA Journals |
| issn | 2049-3614 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Endocrine Connections |
| spelling | doaj-art-9bcd4e26b4f04147ba4d0cc7aa6294982025-08-20T02:20:25ZengBioscientificaEndocrine Connections2049-36142025-04-0114510.1530/EC-24-04701Identification of tryptophan metabolism-related biomarkers for nonalcoholic fatty liver disease through network analysisCuihua Jiang0Jianqi Liang1Kaibo Hu2Yanqing Ye3Jiajia Yang4Xiaozhi Zhang5Guilin Ye6Jing Zhang7Deju Zhang8Bin Zhong9Peng Yu10Liefeng Wang11Bin Zeng12Department of Pain Management, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, ChinaDepartment of Endocrinology and Metabolism, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaDepartment of Endocrinology and Metabolism, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaDepartment of Gastroenterology, First Affiliated Hospital of Gannan Medical University, Ganzhou, ChinaSchool of Basic Medicine, Gannan Medical University, Ganzhou, ChinaSchool of Basic Medicine, Gannan Medical University, Ganzhou, ChinaSchool of Basic Medicine, Gannan Medical University, Ganzhou, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaFood and Nutritional Sciences, School of Biological Sciences, The University of Hong Kong, Hong Kong, ChinaDepartment of Pharmacy, First Affiliated Hospital of Gannan Medical University, Ganzhou, ChinaDepartment of Endocrinology and Metabolism, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaSchool of Basic Medicine, Gannan Medical University, Ganzhou, ChinaDepartment of Gastroenterology, First Affiliated Hospital of Gannan Medical University, Ganzhou, ChinaBackground: Increasing evidence demonstrates that tryptophan metabolism is closely related to the development of nonalcoholic fatty liver disease (NAFLD). This study aimed to identify specific biomarkers of NAFLD associated with tryptophan metabolism and research its functional mechanism. Methods: We downloaded NAFLD RNA-sequencing data from GSE89632 and GSE24807, and obtained tryptophan metabolism-related genes (TMRGs) from the MsigDB database. The R package limma and WGCNA were used to identify TMRGs–DEGs, and GO, KEGG and Cytoscape were used to analyze and visualize the data. Immune cell infiltration analysis was used to explore the immune mechanism of NAFLD and the biomarkers. We also validated extended levels of biomarkers. Results: We identified 375 NAFLD differentially expressed genes (DEGs) and 85 TMRGs–DEGs. GO/KEGG analysis revealed that TMRGs–DEGs were mainly enriched in triglyceride and cholesterol metabolism. ROC curves identified CCL20 (AUC = 0.917), CD160 (AUC = 0.933) and CYP7A1 (AUC = 1) as biomarkers of NAFLD. Immune infiltration analysis showed significant differences in ten immune cells, and the activation of dendritic cells and mast cells were highly positively correlated with NAFLD. CCL20, CD160 and CYP7A1 were highly correlated with M2 macrophage, neutrophil and mast cells activation, respectively. Twenty-seven TMRGs correlated with hub genes, and gene set enrichment analysis demonstrated their function in tryptophan- and lysine-containing metabolic process. We identified 41 therapeutic drug matches which corresponded to two hub genes and four drugs which co-targeted CCL20 and CYP7A1. Finally, three hub genes were validated in our mouse model. Conclusions: CCL20, CD160 and CYP7A1 are tryptophan metabolism-related biomarkers of NAFLD, related to glycerol ester and cholesterol metabolism. We screened four compounds which co-target CCL29 and CYP7A1 to provide potential experimental drugs for NAFLD.https://ec.bioscientifica.com/view/journals/ec/14/5/EC-24-0470.xmlnonalcoholic fatty liver diseasetryptophan metabolismbiomarkersmachine learningnetwork analysis |
| spellingShingle | Cuihua Jiang Jianqi Liang Kaibo Hu Yanqing Ye Jiajia Yang Xiaozhi Zhang Guilin Ye Jing Zhang Deju Zhang Bin Zhong Peng Yu Liefeng Wang Bin Zeng Identification of tryptophan metabolism-related biomarkers for nonalcoholic fatty liver disease through network analysis Endocrine Connections nonalcoholic fatty liver disease tryptophan metabolism biomarkers machine learning network analysis |
| title | Identification of tryptophan metabolism-related biomarkers for nonalcoholic fatty liver disease through network analysis |
| title_full | Identification of tryptophan metabolism-related biomarkers for nonalcoholic fatty liver disease through network analysis |
| title_fullStr | Identification of tryptophan metabolism-related biomarkers for nonalcoholic fatty liver disease through network analysis |
| title_full_unstemmed | Identification of tryptophan metabolism-related biomarkers for nonalcoholic fatty liver disease through network analysis |
| title_short | Identification of tryptophan metabolism-related biomarkers for nonalcoholic fatty liver disease through network analysis |
| title_sort | identification of tryptophan metabolism related biomarkers for nonalcoholic fatty liver disease through network analysis |
| topic | nonalcoholic fatty liver disease tryptophan metabolism biomarkers machine learning network analysis |
| url | https://ec.bioscientifica.com/view/journals/ec/14/5/EC-24-0470.xml |
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