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Candidate urine biomarker discovery from only five pairs of samples before and after tumor resection in glioma patients

Jianqiang Wu, Jun Zhang, Yuanli Zhao, Youhe Gao
doi: https://doi.org/10.1101/240861
Jianqiang Wu
1National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China;
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Jun Zhang
2Department of Neurosurgery, Peking University International Hospital, Peking University, Beijing, China;
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Yuanli Zhao
2Department of Neurosurgery, Peking University International Hospital, Peking University, Beijing, China;
3Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University; China National Clinical Research Center for Neurological Diseases, Beijing, China;
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  • For correspondence: zhaoyuanli@126.com gaoyouhe@bnu.edu.cn
Youhe Gao
4Department of Biochemistry and Molecular Biology, School of Life Sciences, Beijing Normal University, Gene Engineering Drug and Biotechnology Beijing Key Laboratory, Beijing, China
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  • For correspondence: zhaoyuanli@126.com gaoyouhe@bnu.edu.cn
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Abstract

Biomarkers are measurable changes associated with the disease. Without the control of homeostatic mechanisms, urine accumulates systemic body changes and thus serves as an excellent early biomarker source. However, urine is affected by many factors other than disease. Although many candidate biomarkers have been identified in animal models, a large number of clinical samples might still be required for the disease related changes. A self-controlled study should be able to avoid the interferences of individual differences among patients. Gliomas are the most common primary malignant brain tumors and have a very poor prognosis. Early diagnosis of gliomas and the monitoring of tumor recurrence are crucial to improve glioma patient outcomes. Here we set to try if biomarker candidates can be identified by comparing urine samples from five glioma patients collected at the time of tumor diagnosis and after surgical removal of the tumor. Using label-free liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) quantification, twenty-seven urinary proteins were significantly changed after tumor resection (fold change ≥ 1.5, P-value < 0.05, and similar changes in all 5 patients), many of which have been previously associated with gliomas, such as CEACAM1, ANXA7, CALR, CRYAB, CD276, pIgR and cathepsin D. Functions of these proteins were significantly enriched in the regulation of tissue remodeling, autophagy, the inhibition of gene expression, the positive regulation of natural killer cell-mediated cytotoxicity and angiogenesis, which are associated with glioma development. Our results suggested that using the self-control of before and after tumor resection is an effective method to identify differential proteins associated with the disease, even with a small number of patients.

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Posted January 02, 2018.
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Candidate urine biomarker discovery from only five pairs of samples before and after tumor resection in glioma patients
Jianqiang Wu, Jun Zhang, Yuanli Zhao, Youhe Gao
bioRxiv 240861; doi: https://doi.org/10.1101/240861
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Candidate urine biomarker discovery from only five pairs of samples before and after tumor resection in glioma patients
Jianqiang Wu, Jun Zhang, Yuanli Zhao, Youhe Gao
bioRxiv 240861; doi: https://doi.org/10.1101/240861

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