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Abstract
The urokinase-type plasminogen activator(PLAU) and its receptor PLAUR participate in a series of cell physiological activities on the extracellular surface. Abnormal expression of PLAU and PLAUR is associated with tumorigenesis. This study aims to evaluate the prognostic value of PLAU/PLAUR transcription expression in glioma and to explore how they affect the generation and progression of glioma. In this study, online databases are applied, such as Oncomine, GEPIA, CGGA, cBioPortal, and LinkedOmics. Overexpression of PLAU/PLAUR was found to be significantly associated with clinical variables including age, tumor type, WHO grade, histology, IDH-1 mutation, and 1p19q status. PLAU and PLAUR had a high correlation in transcriptional expression levels. High expression of PLAU and PLAUR predicted a poor prognosis in primary glioma and recurrent glioma patients, especially in lower grade gliomas. Cox regression analysis indicated that high expression of PLAU and PLAUR were independent prognostic factors for shorter overall survival in glioma patients. In gene co-expression network analysis PLAU and PLAUR and their co-expression genes were found to be involved in inflammatory activities and tumor-related signaling pathways. In conclusion, PLAU and PLAUR could be promising prognostic biomarkers and potential therapeutic targets of glioma patients.
Highlights
Glioma, a broad category of brain tumors with high fatality rate, is the most common type among primary malignant brain tumors in adults, though accounting for less than 1% of all newly diagnosed tumors [1]
PLAU, by binding to PLAUR which is located on the extracellular surface, activates a cascade of extracellular proteases, which are involved in matrix remodeling and cell migration
High transcriptional levels of PLAU and PLAUR have been discovered in various tumors and have predicted a poor prognosis among the patients [12, 35,36,37]
Summary
A broad category of brain tumors with high fatality rate, is the most common type among primary malignant brain tumors in adults, though accounting for less than 1% of all newly diagnosed tumors [1]. Among all kinds of diffuse glioma, 70-75% of them are glioblastoma(GBM), which is the most fatal one, with a median overall survival less than 2 years after standard chemoradiotherapy. Molecular therapy that targets epigenetic alterations is under evaluation and is supposed to lead to an important breakthrough in the treatment of malignancies like GBM [2]. Biomarkers like isocitrate dehydrogenase 1(IDH-1) and O6-methylguanine-DNA methyltransferase (MGMT) play a crucial role in diagnosis and prognosis and work as potential therapeutic targets. A deeper research of these biomarkers provides an essential framework to treat particular glioma subtypes [4]
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