title: Phospholipase C Beta 1: a Candidate Signature Gene for Proneural Subtype High-Grade Glioma.
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.
authors.affiliation: The Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center at Houston (UTHealth) Medical School, 6400 Fannin Street, Suite 2800, Houston, TX, 77030, USA.
authors.forename: Guangrong
authors.initials: G
authors.lastname: Lu
authors.affiliation: The Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston (UTHealth) Medical School, Houston, TX, 77030, USA.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Chang
authors.affiliation: Division of Biostatistics, UTHealth School of Public Health, Houston, TX, 77030, USA.
authors.forename: Zheyu
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Division of Biostatistics, UTHealth School of Public Health, Houston, TX, 77030, USA.|Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: The Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center at Houston (UTHealth) Medical School, 6400 Fannin Street, Suite 2800, Houston, TX, 77030, USA.|The Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston (UTHealth) Medical School, Houston, TX, 77030, USA.|Department of Medicine and Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: The Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center at Houston (UTHealth) Medical School, 6400 Fannin Street, Suite 2800, Houston, TX, 77030, USA. jay.jiguang.zhu@uth.tmc.edu.
authors.forename: Jay-Jiguang
authors.initials: JJ
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D005910:Glioma / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D020411:Oligonucleotide Array Sequence Analysis; D054799:Phospholipase C beta / Q000235:genetics*; D015203:Reproducibility of Results
chemical_list: D054799:Phospholipase C beta
keywords: Biomarker; Glioblastoma; Glioma; PLCβ1; Proneural; REMBRANDT; Signature gene; TCGA