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 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.

A Novel Classifier Based on Urinary Proteomics for Distinguishing Between Benign and Malignant Ovarian Tumors

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Effects of Donor-Recipient Age Difference in Renal Transplantation, an Investigation on Renal Function and Fluid Proteome

“…The following filter was used in this study, 1% false-positive rate at protein level and each protein with ≥1 unique peptides and protein areas were used for protein quantification. 11 , 12 After filtering the results by above filter, proteins were exported for proteomic analysis workflow described here.…”

Diagnosis of Glioma Molecular Markers by Terahertz Technologies

“…Informative urinary biomarkers of glioma have been analyzed [68][69][70]. A biomarker panel consisting of Alpha-1-antichymotrypsin (AACT), Thrombospondin-4, Malate dehydrogenase mitochondrial, Calreticulin, Galectin-1 (LEG1), and Alpha-2-HS-glycoprotein (AHSG) showed the best glioma diagnosis accuracy, with an area under the curve value of 0.96, as well as the sensitivity and specificity of 0.9 and 0.92, respectively [68]. AACT, LEG1, and AHSG are also potential cerebrospinal fluid or blood biomarkers of gliomas.…”