HR-MS Based Untargeted Lipidomics Reveals Characteristic Lipid Signatures of Wilson’s Disease
Background and Aims: The diagnosis of Wilson’s disease (WD) is challenging by clinical or genetic criteria. A typical early pathological change of WD is the increased liver lipid deposition and lowered serum triglyceride (TG). Therefore, the contents of serum lipids may provide evidence for screenin...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:cda7399bff9c4d8cb229bd3552efbf382021-11-22T05:58:22ZHR-MS Based Untargeted Lipidomics Reveals Characteristic Lipid Signatures of Wilson’s Disease1663-981210.3389/fphar.2021.754185https://doaj.org/article/cda7399bff9c4d8cb229bd3552efbf382021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.754185/fullhttps://doaj.org/toc/1663-9812Background and Aims: The diagnosis of Wilson’s disease (WD) is challenging by clinical or genetic criteria. A typical early pathological change of WD is the increased liver lipid deposition and lowered serum triglyceride (TG). Therefore, the contents of serum lipids may provide evidence for screening of biomarkers for WD.Methods: 34 WD patients, 31 WD relatives, and 65 normal controls were enrolled in this study. Serum lipidomics data was acquired by an ultra-high-performance liquid chromatography high-resolution mass spectrometry system, and the data were analyzed by multivariate statistical methods.Results: Of all 510 identified lipids, there are 297 differential lipids between the WD and controls, 378 differential lipids between the relatives and controls, and 119 differential lipids between the patients and relatives. In WD, the abundances of most saturated TG were increased, whereas other unsaturated lipids decreased, including phosphatidylcholine (PC), sphingomyelin (SM), lysophosphatidylcholine (LPC), ceramide (Cer), and phosphatidylserine (PS). We also found many serum lipid species may be used as biomarkers for WD. The areas under the receiver operating characteristic curve (AUC) of PS (35:0), PS (38:5), and PS (34:0) were 0.919, 0.843, and 0.907. The AUCs of TG (38:0) and CerG1 (d42:2) were 0.948 and 0.915 and the AUCs of LPC (17:0) and LPC (15:0) were 0.980 and 0.960, respectively. The lipid biomarker panel exhibits good diagnostic performance for WD. The correlation networks were built among the different groups and the potential mechanisms of differential lipids were discussed. Interestingly, similar lipid profile of WD is also found in their relatives, which indicated the changes may also related to the mutation of the ATP7B gene.Conclusions: Lipid deregulation is another important hallmark of WD besides the deposition of copper. Our lipidomic results provide new insights into the diagnostic and therapeutic targets of WD.Yixiao ZhiYixiao ZhiYujiao SunYujiao SunYonggeng JiaoChen PanChen PanZeming WuChang LiuChang LiuJie SuJie ZhouDong ShangDong ShangDong ShangJunqi NiuRui HuaPeiyuan YinPeiyuan YinFrontiers Media S.A.articleWilson diseaselipidomicsbiomarkerstriglyceridemetabolomicTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021) |
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DOAJ |
| collection |
DOAJ |
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EN |
| topic |
Wilson disease lipidomics biomarkers triglyceride metabolomic Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
Wilson disease lipidomics biomarkers triglyceride metabolomic Therapeutics. Pharmacology RM1-950 Yixiao Zhi Yixiao Zhi Yujiao Sun Yujiao Sun Yonggeng Jiao Chen Pan Chen Pan Zeming Wu Chang Liu Chang Liu Jie Su Jie Zhou Dong Shang Dong Shang Dong Shang Junqi Niu Rui Hua Peiyuan Yin Peiyuan Yin HR-MS Based Untargeted Lipidomics Reveals Characteristic Lipid Signatures of Wilson’s Disease |
| description |
Background and Aims: The diagnosis of Wilson’s disease (WD) is challenging by clinical or genetic criteria. A typical early pathological change of WD is the increased liver lipid deposition and lowered serum triglyceride (TG). Therefore, the contents of serum lipids may provide evidence for screening of biomarkers for WD.Methods: 34 WD patients, 31 WD relatives, and 65 normal controls were enrolled in this study. Serum lipidomics data was acquired by an ultra-high-performance liquid chromatography high-resolution mass spectrometry system, and the data were analyzed by multivariate statistical methods.Results: Of all 510 identified lipids, there are 297 differential lipids between the WD and controls, 378 differential lipids between the relatives and controls, and 119 differential lipids between the patients and relatives. In WD, the abundances of most saturated TG were increased, whereas other unsaturated lipids decreased, including phosphatidylcholine (PC), sphingomyelin (SM), lysophosphatidylcholine (LPC), ceramide (Cer), and phosphatidylserine (PS). We also found many serum lipid species may be used as biomarkers for WD. The areas under the receiver operating characteristic curve (AUC) of PS (35:0), PS (38:5), and PS (34:0) were 0.919, 0.843, and 0.907. The AUCs of TG (38:0) and CerG1 (d42:2) were 0.948 and 0.915 and the AUCs of LPC (17:0) and LPC (15:0) were 0.980 and 0.960, respectively. The lipid biomarker panel exhibits good diagnostic performance for WD. The correlation networks were built among the different groups and the potential mechanisms of differential lipids were discussed. Interestingly, similar lipid profile of WD is also found in their relatives, which indicated the changes may also related to the mutation of the ATP7B gene.Conclusions: Lipid deregulation is another important hallmark of WD besides the deposition of copper. Our lipidomic results provide new insights into the diagnostic and therapeutic targets of WD. |
| format |
article |
| author |
Yixiao Zhi Yixiao Zhi Yujiao Sun Yujiao Sun Yonggeng Jiao Chen Pan Chen Pan Zeming Wu Chang Liu Chang Liu Jie Su Jie Zhou Dong Shang Dong Shang Dong Shang Junqi Niu Rui Hua Peiyuan Yin Peiyuan Yin |
| author_facet |
Yixiao Zhi Yixiao Zhi Yujiao Sun Yujiao Sun Yonggeng Jiao Chen Pan Chen Pan Zeming Wu Chang Liu Chang Liu Jie Su Jie Zhou Dong Shang Dong Shang Dong Shang Junqi Niu Rui Hua Peiyuan Yin Peiyuan Yin |
| author_sort |
Yixiao Zhi |
| title |
HR-MS Based Untargeted Lipidomics Reveals Characteristic Lipid Signatures of Wilson’s Disease |
| title_short |
HR-MS Based Untargeted Lipidomics Reveals Characteristic Lipid Signatures of Wilson’s Disease |
| title_full |
HR-MS Based Untargeted Lipidomics Reveals Characteristic Lipid Signatures of Wilson’s Disease |
| title_fullStr |
HR-MS Based Untargeted Lipidomics Reveals Characteristic Lipid Signatures of Wilson’s Disease |
| title_full_unstemmed |
HR-MS Based Untargeted Lipidomics Reveals Characteristic Lipid Signatures of Wilson’s Disease |
| title_sort |
hr-ms based untargeted lipidomics reveals characteristic lipid signatures of wilson’s disease |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/cda7399bff9c4d8cb229bd3552efbf38 |
| work_keys_str_mv |
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| _version_ |
1718418128037216256 |