Phospholipase C Beta 1: a Candidate Signature Gene for Proneural Subtype High-Grade Glioma

• DOI: 10.1007/s12035-015-9518-2
• Publication Date: 2015-11-28T01:55:18Z
• Authors: Guangrong Lu; Jeffrey T. Chang; Zheyu Liu; Yong Chen; Min Li; Jay-Jiguang Zhu
• Keywords: Adult; Male; 0301 basic medicine; Brain Neoplasms; Gene Expression Profiling; Phospholipase C beta; Reproducibility of Results; Glioma; Kaplan-Meier Estimate; Middle Aged; Article; Gene Expression Regulation, Enzymologic; 3. Good health; Cohort Studies; Gene Expression Regulation, Neoplastic; Cellular and Molecular Neuroscience; 03 medical and health sciences; Humans; Female; Neoplasm Grading; Genetic Association Studies; Aged; Oligonucleotide Array Sequence Analysis

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.