Abstract
Phospholipase C beta 1 (PLCβ1) expresses in gliomas and cultured glial cells, but its expression is barely detectable in normal glial cells. We analyzed data from Gene Expression Omnibus (GEO-GDSxxx), The Cancer Genome Atlas (TCGA), and the Repository for Molecular Brain Neoplasia Data (REMBRANDT) to explore the potential role of PLCβ1 as a biomarker in high-grade glioma (HGG). PLCβ1 expression is significantly higher in grade III gliomas than that in grade IV gliomas from GDS1815 (n = 24 vs. 76), GDS1962 (n = 19 vs. 81), and GDS1975 (n = 26 vs. 59). In GDS1815, PLCβ1 expression correlates with several known proneural (PN) signature genes; its expression from PN subtype (n = 15) is significantly higher than that from mesenchymal (Mes) subtype (n = 33) HGG. In GDS1962, PLCβ1 expression is the highest in nontumor brain tissue (n = 23) and is significantly higher than its expression in grade II gliomas [astrocytomas (n = 7) and oligodendrogliomas (n = 37)]. A Kaplan-Meier survival curve from a REMBRANDT cohort demonstrates that glioma patients with intermediate PLCβ1 expression (n = 103) survived significantly longer than PLCβ1 downregulated (2X) groups (n = 226). From TCGA data, PLCβ1 RNA-Seq signal inversely correlates with the pathological grades, and PLCβ1 expression in PN (n = 8) is of significantly higher levels than that in Mes (n = 8) subtypes of glioblastoma. The top 50 % of PLCβ1 expression subgroup (n = 294) of gliomas (grades II to IV merged) survived significantly longer than the low 50 percentile of the PLCβ1 expression subgroup (n = 293). p values are less than 0.05 for all these analyses. We conclude that PLCβ1 is a candidate signature gene for PN subtype HGG, and its expression inversely correlates with glioma pathological grade and is a potential prognostic factor.Electronic supplementary materialThe online version of this article (doi:10.1007/s12035-015-9518-2) contains supplementary material, which is available to authorized users.
Highlights
Gliomas are the most common primary brain tumors, and the pathologic grade is the most important factor determining patients’ prognosis [1, 2]
Our study provides evidence for the first time that PLCβ1 is a candidate signature gene for PN subtype of high-grade gliomas (HGG)
Previous research has highly recommended integrating molecular findings in current World Health Organization (WHO) classifications in order to generate a new histomolecular classification guideline [3, 8]
Summary
Gliomas are the most common primary brain tumors, and the pathologic grade is the most important factor determining patients’ prognosis [1, 2]. Grades I/II and III/IV are collectively referred to as low- (LGG) and high-grade gliomas (HGG), Mol Neurobiol (2016) 53:6511–6525 respectively. Grade IV gliomas, known as glioblastoma multiforme (GBM), are the most common and the most malignant type of primary brain tumor and account for 50–60 % of all gliomas [4]. Patients can develop gliomas at any age; LGGs are more often found in children and young adults and HGGs are more prevalent in the elderly. Other known prognostic factors include patient’s age at initial diagnosis, extent of tumor resection, and Karnofsky performance score [1, 5]
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