MPTH-19PHOSPHOLIPASE C BETA 1: A CANDIDATE SIGNATURE GENE FOR PRONEURAL SUBTYPE HIGH-GRADE GLIOMA

Abstract

BACKGROUND: Phospholipase C beta 1 (PLCβ1) expresses in glioma tissue and cultured glial cells, but barely detectable in normal glial cells. Whether PLCβ1 gene expression plays a pathological role in glioma has not been studied. METHODS: We analyzed data from Gene Expression Omnibus (GEO-GDSxxx), The Cancer Genome Atlas (TCGA), and the Repository for Molecular Brain Neoplasia Data (REMBRANDT) to investigate the potential role of PLCβ1 in high-grade glioma (HGG). RESULTS: In GDS1815, PLCβ1 expression correlates with known proneural (PN) signature genes; its expression level from PN subtype (n = 15) is significantly higher than that from mesenchymal (Mes) subtype (n = 33) HGG (p < 0.001). Furthermore, PLCβ1 expression is significantly higher in grade III than in grade IV gliomas from GDS1815 (n = 24 vs. 76), GDS1962 (n = 19 vs. 81), and GDS1975 (n = 26 vs. 59); ultimately, p < 0.05 for all. In GDS1962, the PLCβ1 expression is highest in non-tumor brain tissue (n = 23) and is significantly higher than that in grade II astrocytomas (n = 7) and oligodendrogliomas (n = 37; p < 0.05 for both. PLCβ1 expression is also higher in low-grade (n = 8) than in high-grade astrocytomas (n = 6) in GDS2853 (p < 0.001). A Kaplan-Meier survival plot from a REMBRANDT cohort demonstrates that astrocytoma and glioma patients with intermediate levels of PLCβ1 expression (n = 45 and 103, respectively) survived significantly longer than down-regulated (2X) PLCβ1 groups (n = 57 and 226, respectively; p < 0.001). From TCGA data, PLCβ1 RNA-Seq signal inversely correlates with the pathological grades and higher levels of PLCβ1 expression in PN (n = 8) than in Mes (n = 8) subtypes of glioblastoma (p < 0.05). The top 50% of PLCβ1 expression subgroup (n = 294) of glioma cases (grade II to IV merged) survived significantly longer time than the low 50%-ile of the PLCβ1 expression subgroup (n = 293; p < 0.001). CONCLUSIONS: PLCβ1 is a candidate signature gene for PN subtype HGG, its expression inversely correlates with glioma pathological grade and is a potential prognosis factor.