2. Academic Validation
  3. HR-MS Based Untargeted Lipidomics Reveals Characteristic Lipid Signatures of Wilson's Disease

HR-MS Based Untargeted Lipidomics Reveals Characteristic Lipid Signatures of Wilson's Disease

  • Front Pharmacol. 2021 Nov 22:12:754185. doi: 10.3389/fphar.2021.754185.
Yixiao Zhi 1 2,  Yujiao Sun 1 3,  Yonggeng Jiao 4,  Chen Pan 1 5,  Zeming Wu 6,  Chang Liu 1 3,  Jie Su 2,  Jie Zhou 2,  Dong Shang 1 2 5,  Junqi Niu 2,  Rui Hua 2,  Peiyuan Yin 1 3
Affiliations

Affiliations

  • 1 Clinical Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, China.
  • 2 Department of Hepatology, The First Hospital of Jilin University, Changchun, China.
  • 3 Institute of Integrative Medicine, Dalian Medical University, Dalian, China.
  • 4 Department of Anesthesiology Jilin Province FAW General Hospital, Changchun, China.
  • 5 Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, China.
  • 6 iPhenome biotechnology Inc. Dalian (Yun Pu Kang), Dalian, China.
PMID: 34880754 DOI: 10.3389/fphar.2021.754185
Abstract

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.

Keywords

Wilson disease; biomarkers; lipidomics; metabolomic; triglyceride.

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