Table 2.
Top 15 gene changes in CD133− GBM daughter cells compared to CD133+ GBM daughter cells sorted from the same CD133+ GBM sphere cultures
| Gene | Symbol | Gene I.D. | Fold change | P value | Functional involvement |
|---|---|---|---|---|---|
| A. Genes upregulated in CD133− D431 GBM daughter cells | |||||
| Integrin-binding sialoprotein | 3381 | IBSP | 10.13 | 0.01969 | A major structural protein of the bone matrices; angiogenesis |
| Chitinase 3-like 1 (cartilage glycoprotein-39) | 1116 | CHI3L1 | 6.93 | 0.039091 | Chondrogenesis, glioblastoma progression marker |
| Tryptophan 2,3-dioxygenase | 6999 | TDO2 | 5.62 | 0.00191 | Enzyme involved in tryptophan catabolism |
| Fibronectin 1 | 2335 | FN1 | 4.61 | 0.039285 | Binds to integrins/extracellular matrix; promote tumor growth |
| Carbonic anhydrase XII | 771 | CA12 | 3.84 | 0.048487 | Acidification of the extracellular milieu; a biomarker of gliomas |
| Hydroxysteroid (11-beta) dehydrogenase 1 | 3290 | HSD11B1 | 3.75 | 0.013701 | Catalyzes the interconversion of inactive cortisone to active cortisol |
| Solute carrier family 7 | 23428 | SLC7A8 | 3.63 | 0.005935 | Transport of neutral amino acids/essential amino acids |
| Stonin 2 | 85439 | STON2 | 3.55 | 0.020396 | A component of the endocytic machinery; regulates vesicle endocytosis |
| Plexin A4, A | 57671 | PLXNA4 | 3.48 | 0.039696 | Mediates multiple semaphorin signals and regulates axon guidance |
| Calcium/calmodulin-dependent protein kinase II inhibitor 1 | 55450 | CAMK2N1 | 3.42 | 0.011008 | Inhibit brain CaM-kinase II activity |
| Anthrax toxin receptor 1 | 84168 | ANTXR1 | 3.28 | 0.031259 | Mediates cell spreading by coupling extracellular ligands to the actin |
| Growth differentiation factor 15 | 9518 | GDF15 | 3.06 | 0.004578 | Tissue differentiation and maintenance |
| Matrix metallopeptidase 14 (membrane-inserted) | 4323 | MMP14 | 3.03 | 0.01905 | Angiogenesis, tumor invasion |
| Elastin microfibril interfacer 1 | 11117 | EMILIN1 | 3.02 | 0.029463 | Extracellular matrix constituent associated with elastic fibers |
| Tissue factor pathway inhibitor | 3675 | TFPI | 3.02 | 0.000305 | Regulates the coagulation pathway; dynamic conduction of blood |
| B. Genes downregulated in CD133− D431 GBM daughter cells | |||||
| Prominin 1/CD133 | 8842 | PROM1 | −8.19 | 0.004998 | Membrane protuberances and cell polarity |
| Glutamate receptor, ionotrophic, AMPA 4 | 2893 | GRIA4 | −4.03 | 0.007852 | Excitatory neurotransmitter receptors |
| v-Myc myelocytomatosis viral related oncogene | 4613 | MYCN | −3.91 | 0.006193 | Embryonal tumor initiation factor |
| PRKC, apoptosis, WT1, regulator | 5074 | PAWR | −3.64 | 0.001191 | Tumor suppressor; apoptosis induction |
| Ksp37 protein | 83888 | KSP37 | −3.46 | 0.016226 | Protein produced by CD4 and cytotoxic lymphocytes |
| Sidekick homolog 2 (chicken) | 54549 | SDK2 | −3.43 | 0.011413 | Cell adhesion protein that guides axonal terminals |
| Frizzled-related protein | 2487 | FRZB | −3.38 | 0.00987 | Antagonizes Wnt pathway |
| Cytoplasmic FMR1 interacting protein 2 | 26999 | CYFIP2 | −3.37 | 0.002989 | A direct p53 target gene; cellular apoptosis |
| Monooxygenase, DBH-like 1 | 26002 | MOXD1 | −3.31 | 0.006728 | Predicted to hydroxylate a substrate in the endoplasmic reticulum |
| Complement factor H | 3075 | CFH | −3.13 | 0.011463 | Inhibition of complement activation |
| Activated leukocyte cell adhesion molecule | 29995 | ALCAM | −3.08 | 0.002511 | Marker of mesenchymal/colorectal cancer stem cells; growth control |
| LIM and cysteine-rich domains 1 | 214 | LMCD1 | −3.08 | 0.007018 | Represses GATA6 in the maintenance of the differentiated phenotype |
| Scrapie responsive protein 1 | 11341 | SCRG1 | −2.98 | 0.010901 | Mesenchymal chondrogenesis, growth suppression |
| v-Myb myeloblastosis viral oncogene homolog (avian) | 4602 | MYB | −2.97 | 0.049344 | Intrinsic factor for neural progenitor cell proliferation |
| Cholinergic receptor, nicotinic, alpha polypeptide 3 | 1136 | CHRNA5 | −2.97 | 0.016751 | Ligand-binding subunit of the ganglionic type nicotinic receptor |
| C. Genes upregulated in CD133− S496 GBM daughter cells | |||||
| 3-Hydroxy-3-methylglutaryl-Coenzyme A synthase 1 | 3157 | HMGCS1 | 3.09 | 0.020826 | Cholesterologenesis |
| Solute carrier family 7 | 23428 | SLC7A8 | 2.87 | 0.035311 | Transport of neutral amino acids/essential amino acids |
| Mitochondrial ribosomal protein L30 | 51263 | MRPL30 | 2.60 | 0.00943 | Protein synthesis within the mitochondrion |
| mRNA turnover 4 homolog | 51154 | MRTO4 | 2.56 | 0.007082 | mRNA turnover and ribosome assembly |
| CCAAT/enhancer binding protein zeta | 10153 | CEBPZ | 2.31 | 0.010864 | Maintains differentiated state; enhances osteoblastic differentiation |
| v-Rel reticuloendotheliosis viral oncogene homolog A | 5970 | RELA | 2.25 | 0.007044 | Cell survival, antiapoptosis |
| Endothelin 3 | 1908 | EDN3 | 2.01 | 0.04014 | Promotes neural crest cell and precursor proliferation |
| Guanine nucleotide binding protein-like 3 (nucleolar)-like | 54552 | GNL3L | 1.89 | 0.022775 | Processing of nucleolar preribosomal RNA |
| Adaptor-related protein complex 1, sigma 2 subunit | 8905 | AP1S2 | 1.89 | 0.03494 | Protein sorting and assembly of endocytic vesicles |
| Protein kinase, cAMP-dependent, catalytic, beta | 5567 | PRKACB | 1.62 | 0.04107 | Proliferation and differentiation; c-myc target gene; tumorigenesis |
| SLIT-ROBO Rho GTPase activating protein 3 | 9901 | SRGAP3 | 1.55 | 0.038237 | Negatively regulates cell migration |
| Integrin, beta 8 | 3696 | ITGB8 | 1.55 | 0.042396 | Brain vascular morphogenesis in the developing CNS |
| Monoamine oxidase A | 4128 | MAOA | 1.53 | 0.034433 | Degrades amine neurotransmitters |
| Phosphoinositide-3-kinase, class 2, beta polypeptide | 5287 | PIK3C2B | 1.53 | 0.034433 | Proliferation, survival; intracellular vesicle transport |
| Baculoviral IAP repeat-containing 4 | 331 | XIAP | 1.52 | 0.022379 | Blocks the apoptosis pathway via inhibiting caspase-3, 7, and 9 |
| D. Genes downregulated in CD133− S496 GBM daughter cells | |||||
| Prominin 1/CD133 | 8842 | PROM1 | −11.00 | 0.039802 | Membrane protuberances and cell polarity |
| Phosphorylase kinase, gamma 2 (testis) | 5261 | PHKG2 | −5.95 | 0.008141 | Activates glycogen phosphorylase |
| BH-protocadherin (brain–heart) | 5099 | PCDH7 | −2.86 | 0.013744 | Calcium-dependent cell–cell adhesion |
| Inhibin, beta A (activin A, activin AB alpha polypeptide) | 3624 | INHBA | −2.82 | 0.026005 | Tooth development; tumor suppressor |
| Melanoma cell adhesion molecule | 4162 | MCAM | −2.81 | 0.013207 | Putative adhesion molecule in neural crest cells/melanoma |
| Low density lipoprotein-related protein 1 | 4035 | LRP1 | −2.75 | 0.018718 | Lipid metabolism; antigrowth, tumor suppressor |
| Leucine rich repeat neuronal 6C | 158038 | LINGO2 | −2.69 | 0.014473 | Expressed in limbic system and neocortex |
| AF4/FMR2 family, member 3 | 3899 | AFF3 | −2.68 | 0.008324 | Regulation of lymphoid development |
| Nephronectin | 255743 | NPNT | −2.65 | 0.013665 | Tumor suppressor |
| ADAM metallopeptidase with thrombospondin type 1 motif 1 | 9510 | ADAMTS1 | −2.60 | 0.017533 | Antiangiogenesis |
| Forkhead box C1 | 2296 | FOXC1 | −2.59 | 0.022414 | Arrests cells in the G0/G1 phase; tumor suppressor |
| AT rich interactive domain 1A (SWI-like) | 8289 | ARID1A | −2.56 | 0.029044 | Differentiation-associated cell cycle arrest; tumor suppressor |
| Solute carrier family 4, anion exchanger, member 2 | 6522 | SLC4A2 | −2.52 | 0.025985 | Housekeeping regulator of intracellular pH; tumor suppressor |
| La ribonucleoprotein domain family, member 1 | 23367 | LARP1 | −2.51 | 0.01622 | Protects the 3′ end of nascent small RNAs from exonuclease digestion |
| Collagen, type IV, alpha 2 | 1284 | COL4A2 | −2.42 | 0.008793 | Inhibits angiogenesis and tumor growth |
Analysis was based on a cutoff of 1.5-fold changes in relative expression compared to CD133+ GBM daughter cells (P < 0.05)