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Published on: July 14, 2017
Identification and validation of argininosuccinate synthase as a candidate urinary biomarker for major depressive
Dong Wu1, Yang Peng2, Jian Zhou3
1Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
Background:
Major depressive disorder (MDD) is a debilitating psychiatric mood disorder. However, no objective laboratory-based test is yet available to aid in the diagnosis of this disorder.
Methods:
In order to identify urinary protein biomarker candidates for MDD, the differential proteomic analysis of urine samples from first-episode drug-naïve MDD subjects and healthy controls (HC) was carried out by using two-dimensional gel electrophoresis separation followed by MALDI-TOF/TOF-MS/MS identification. Then, the differential expression levels of some candidate proteins were further validated by immunoblot analysis.
Results:
Through mass spectrometry and database searching, a total of 27 differential proteins were identified, primarily including enzymes, plasma proteins, serpins, and adhesion molecules. Five proteins were selected for subsequent validation by Western blotting. One arginine recycling enzyme - argininosuccinate synthase (ASS1) - was further confirmed to be significantly downregulated in the urine of 30 depressed subjects while remaining unchanged in the plasma. Importantly, receiver-operator curve analyses revealed that ASS1 displayed strong efficacy in distinguishing MDD subjects from HC.
Conclusion:
The present study provides a range of urinary protein biomarker candidates for MDD, and further demonstrates that ASS1 has a potential for clinical diagnosis of this disorder.

