摘要
AbstractBackground: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.
机构地区
Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China,Department of Neurosurgery, Peking University International Hospital, Peking University, Beijing 102206, China,Department of Biochemistry, Gene Engineering Drug and Biotechnology Beijing Key Laboratory, School of Life Sciences, Beijing Normal University, No.19 Xinjiekouwai Street, Beijing 100875, China,Department of Neurosurgery, Peking University International Hospital, Peking University, Beijing 102206, China; Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University; China National Clinical Research Center for Neurological Diseases, Beijing 100050, China
出版日期
2020年08月10日(中国期刊网平台首次上网日期,不代表论文的发表时间)