Urinary biomarker discovery in gliomas using mass spectrometry-based clinical proteomics

Abstract Background Gliomas are the most common primary malignant brain tumors and have a poor prognosis. Early detection of gliomas is crucial to improve patient outcomes. Urine accumulates systematic body changes and thus serves as an excellent early biomarker source. Methods At the biomarker disc...

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Main Authors: Jianqiang Wu, Jun Zhang, Jing Wei, Yuanli Zhao, Youhe Gao
Format: Article
Language:English
Published: BMC 2020-04-01
Series:Chinese Neurosurgical Journal
Subjects:
Online Access:http://link.springer.com/article/10.1186/s41016-020-00190-5
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author Jianqiang Wu
Jun Zhang
Jing Wei
Yuanli Zhao
Youhe Gao
author_facet Jianqiang Wu
Jun Zhang
Jing Wei
Yuanli Zhao
Youhe Gao
author_sort Jianqiang Wu
collection DOAJ
description Abstract Background Gliomas are the most common primary malignant brain tumors and have a poor prognosis. Early detection of gliomas is crucial to improve patient outcomes. Urine accumulates systematic body changes and thus serves as an excellent early biomarker source. Methods At the biomarker discovery phase, we performed a self-controlled proteomics analysis by comparing urine samples collected from five glioma patients at the time of tumor diagnosis and after surgical removal of the tumor. At the biomarker validation phase, we further validated some promising proteins using parallel reaction monitoring (PRM)-based targeted proteomics in another cohort, including glioma, meningioma, and moyamoya disease patients as well as healthy controls. Results Using label-free proteome quantitation (LFQ), we identified twenty-seven urinary proteins that were significantly changed after tumor resection, many of which have been previously associated with gliomas. The functions of these proteins were significantly enriched in the autophagy and angiogenesis, which are associated with glioma development. After targeted proteomics validation, we identified a biomarker panel (AACT, TSP4, MDHM, CALR, LEG1, and AHSG) with an area under the curve (AUC) value of 0.958 for the detection of gliomas. Interestingly, AACT, LEG1, and AHSG are also potential cerebrospinal fluid or blood biomarkers of gliomas. Conclusions Using LFQ and PRM proteome quantification, we identified candidate urinary protein biomarkers with the potential to detect gliomas. This study will also provide clues for future biomarker studies involving brain diseases.
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spelling doaj.art-b81ba796b18044ed894ea7adefcdcc8f2022-12-22T03:03:42ZengBMCChinese Neurosurgical Journal2057-49672020-04-016111010.1186/s41016-020-00190-5Urinary biomarker discovery in gliomas using mass spectrometry-based clinical proteomicsJianqiang Wu0Jun Zhang1Jing Wei2Yuanli Zhao3Youhe Gao4Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Neurosurgery, Peking University International Hospital, Peking UniversityDepartment of Biochemistry, Gene Engineering Drug and Biotechnology Beijing Key Laboratory, School of Life Sciences, Beijing Normal UniversityDepartment of Neurosurgery, Peking University International Hospital, Peking UniversityDepartment of Biochemistry, Gene Engineering Drug and Biotechnology Beijing Key Laboratory, School of Life Sciences, Beijing Normal UniversityAbstract Background Gliomas are the most common primary malignant brain tumors and have a poor prognosis. Early detection of gliomas is crucial to improve patient outcomes. Urine accumulates systematic body changes and thus serves as an excellent early biomarker source. Methods At the biomarker discovery phase, we performed a self-controlled proteomics analysis by comparing urine samples collected from five glioma patients at the time of tumor diagnosis and after surgical removal of the tumor. At the biomarker validation phase, we further validated some promising proteins using parallel reaction monitoring (PRM)-based targeted proteomics in another cohort, including glioma, meningioma, and moyamoya disease patients as well as healthy controls. Results Using label-free proteome quantitation (LFQ), we identified twenty-seven urinary proteins that were significantly changed after tumor resection, many of which have been previously associated with gliomas. The functions of these proteins were significantly enriched in the autophagy and angiogenesis, which are associated with glioma development. After targeted proteomics validation, we identified a biomarker panel (AACT, TSP4, MDHM, CALR, LEG1, and AHSG) with an area under the curve (AUC) value of 0.958 for the detection of gliomas. Interestingly, AACT, LEG1, and AHSG are also potential cerebrospinal fluid or blood biomarkers of gliomas. Conclusions Using LFQ and PRM proteome quantification, we identified candidate urinary protein biomarkers with the potential to detect gliomas. This study will also provide clues for future biomarker studies involving brain diseases.http://link.springer.com/article/10.1186/s41016-020-00190-5GliomaBiomarkersUrineProteomics
spellingShingle Jianqiang Wu
Jun Zhang
Jing Wei
Yuanli Zhao
Youhe Gao
Urinary biomarker discovery in gliomas using mass spectrometry-based clinical proteomics
Chinese Neurosurgical Journal
Glioma
Biomarkers
Urine
Proteomics
title Urinary biomarker discovery in gliomas using mass spectrometry-based clinical proteomics
title_full Urinary biomarker discovery in gliomas using mass spectrometry-based clinical proteomics
title_fullStr Urinary biomarker discovery in gliomas using mass spectrometry-based clinical proteomics
title_full_unstemmed Urinary biomarker discovery in gliomas using mass spectrometry-based clinical proteomics
title_short Urinary biomarker discovery in gliomas using mass spectrometry-based clinical proteomics
title_sort urinary biomarker discovery in gliomas using mass spectrometry based clinical proteomics
topic Glioma
Biomarkers
Urine
Proteomics
url http://link.springer.com/article/10.1186/s41016-020-00190-5
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AT jingwei urinarybiomarkerdiscoveryingliomasusingmassspectrometrybasedclinicalproteomics
AT yuanlizhao urinarybiomarkerdiscoveryingliomasusingmassspectrometrybasedclinicalproteomics
AT youhegao urinarybiomarkerdiscoveryingliomasusingmassspectrometrybasedclinicalproteomics