Microarray Expression Data Identify <i>DCC</i> as a Candidate Gene for Early Meningioma Progression

<div><p>Meningiomas are the most common primary brain tumors bearing in a minority of cases an aggressive phenotype. Although meningiomas are stratified according to their histology and clinical behavior, the underlying molecular genetics predicting aggressiveness are 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 deleted in colorectal cancer (<i>DCC</i>) as a differentially expressed gene (DEG) enabling us to cluster meningiomas into <i>DCC</i> low expression (3 grade I and 3 grade II tumors), <i>DCC</i> medium expression (2 grade I and 1 grade II tumors), and <i>DCC</i> high expression (5 grade I tumors) groups. Comparison between the <i>DCC</i> low expression and <i>DCC</i> high expression groups resulted in 416 DEGs (<i>p</i>-value < 0.05; fold change > 2). The most significantly downregulated genes in the <i>DCC</i> low expression group comprised <i>DCC</i>, phosphodiesterase 1C (<i>PDE1C</i>), calmodulin-dependent 70kDa olfactomedin 2 (<i>OLFM2</i>), glutathione S-transferase mu 5 (<i>GSTM5</i>), phosphotyrosine interaction domain containing 1 (<i>PID1</i>), sema domain, transmembrane domain (TM) and cytoplasmic domain, (semaphorin) 6D (<i>SEMA6D</i>), and indolethylamine N-methyltransferase (<i>INMT</i>). The most significantly upregulated genes comprised chromosome 5 open reading frame 63 (<i>C5orf63</i>), homeodomain interacting protein kinase 2 (<i>HIPK2</i>), and basic helix-loop-helix family, member e40 (<i>BHLHE40</i>). 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 meningiomas from female and male patients and for a comparison between brain invasive and non-invasive meningiomas resulting in a number of significant DEGs and related biofunctions. In conclusion, based on its expression levels, <i>DCC</i> may constitute a valid biomarker to identify those benign meningiomas at risk for progression.</p>