Microarray Expression Data Identify DCC as a Candidate Gene for Early Meningioma Progression.
2016
Meningiomasare the most common primary brain tumors bearing in a minority of cases an aggressive phenotype. Although
meningiomasare stratified according to their histology and clinical behavior, the underlying molecular
geneticspredicting
aggressivenessare not thoroughly understood. We performed whole transcript expression profiling in 10 grade I and four grade II
meningiomas, three of which invaded the brain. Microarray expression analysis identified
deletedin
colorectal cancer(DCC) as a differentially expressed gene (DEG) enabling us to cluster
meningiomasinto DCC low expression (3 grade I and 3 grade II tumors), DCC medium expression (2 grade I and 1 grade II tumors), and DCC high expression (5 grade I tumors) groups. Comparison between the DCC low expression and DCC high expression groups resulted in 416 DEGs (p-value 2). The most significantly downregulated genes in the DCC low expression group comprised DCC, phosphodiesterase 1C (PDE1C), calmodulin-dependent 70kDa
olfactomedin 2(OLFM2), glutathione S-transferase mu 5 (GSTM5), phosphotyrosine interaction domain containing 1 (PID1),
sema domain, transmembrane domain (TM) and cytoplasmic domain, (
semaphorin) 6D (SEMA6D), and
indolethylamine N-methyltransferase(INMT). The most significantly upregulated genes comprised chromosome 5 open reading frame 63 (C5orf63), homeodomain interacting protein kinase 2 (HIPK2), and
basic helix-loop-helixfamily, member e40 (BHLHE40). Biofunctional analysis identified as predicted top upstream regulators beta-estradiol, TGFB1, Tgf beta complex,
LY294002, and dexamethasone and as predicted top regulator effectors NFkB,
PIK3R1, and CREBBP. The microarray expression data served also for a comparison between
meningiomasfrom female and male patients and for a comparison between brain invasive and non-invasive
meningiomasresulting in a number of significant DEGs and related biofunctions. In conclusion, based on its expression levels, DCC may constitute a valid biomarker to identify those benign
meningiomasat risk for progression.
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