Microarray Expression Data Identify DCC as a Candidate Gene for Early Meningioma Progression.
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 (DCC) as a differentially expressed gene (DEG) enabling us to cluster meningiomas into 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<0.05; fold change>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-helix family, 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 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, DCC may constitute a valid biomarker to identify those benign meningiomas at risk for progression.
Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.|KACST Technology Innovation Center in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Hans-Juergen
HJ
Schulten
King Fahad Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
Deema
D
Hussein
Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.|Department of Biology, King Abdulaziz University, Jeddah, Saudi Arabia.
Fatima
F
Al-Adwani
Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.|KACST Technology Innovation Center in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Sajjad
S
Karim
Department of Pathology, Faculty of Medicine, King Abdulaziz University Hospital, Jeddah, Saudi Arabia.|Department of Pathology, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia.
Jaudah
J
Al-Maghrabi
Department of Biology, King Abdulaziz University, Jeddah, Saudi Arabia.
Mona
M
Al-Sharif
Department of Pathology, Faculty of Medicine, King Abdulaziz University Hospital, Jeddah, Saudi Arabia.
Awatif
A
Jamal
Department of Pathology, Faculty of Medicine, King Abdulaziz University Hospital, Jeddah, Saudi Arabia.
Fahad
F
Al-Ghamdi
Division of Neurosurgery, Department of Surgery, King Abdulaziz University Hospital, Jeddah, Saudi Arabia.
Saleh S
SS
Baeesa
Division of Neurosurgery, Department of Surgery, King Abdulaziz University Hospital, Jeddah, Saudi Arabia.
Mohammed
M
Bangash
Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.|KACST Technology Innovation Center in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Adeel
A
Chaudhary
Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.|KACST Technology Innovation Center in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Mohammed
M
Al-Qahtani
D000368:Aged; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D000075389:DCC Receptor; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008579:Meningioma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D011956:Receptors, Cell Surface / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D000075389:DCC Receptor; C501909:DCC protein, human; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins