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

详细信息    查看全文

• 作者：Guangrong Lu ; Jeffrey T. Chang ; Zheyu Liu ; Yong Chen ; Min Li…
• 关键词：PLCβ1 ; Glioma ; Glioblastoma ; Proneural ; Signature gene ; Biomarker ; REMBRANDT ; TCGA
• 刊名：Molecular Neurobiology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：53
• 期：9
• 页码：6511-6525
• 全文大小：1,994 KB
• 刊物主题：Neurosciences; Neurobiology; Cell Biology; Neurology;
• 出版者：Springer US
• ISSN：1559-1182
• 卷排序：53

文摘

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.