Interactions of ligand with the protein.

<p>Red represents protein as cartoon; grey represents interacting side chain as cylinder; and green represents drug as ball and stick model.</p

Canonical pathways predicted by Ingenuity Pathway Analysis for significant genes differentially expressed in kidney cancer.

<p>Canonical pathways predicted by Ingenuity Pathway Analysis for significant genes differentially expressed in kidney cancer.</p

Binding and interaction values for docking of S100A8 dimer and EGFR kinase domain with inhibitors (midostaurin, enzastaurin and gefitinib).

<p>Binding and interaction values for docking of S100A8 dimer and EGFR kinase domain with inhibitors (midostaurin, enzastaurin and gefitinib).</p

Leukocyte Extravasation Signaling: Transcriptomic signatures of kidney cancer showed a significant activation in leukocyte extravasation signaling pathway.

<p>Red represents overexpression and green underexpression.</p

Structure visualization of cancer signaling target proteins S100A8 (1MR8), and EGFR tyrosine kinase domain (2GS2) retrieved from Protein Data Bank.

<p>Surface representation of the two PDB structures used for docking analysis. Figure made using PyMol. (1) MR8 chain A (green) + chain B (cyan) (2) 2GS2 chain (yellow), drug binding cavity in magenta.</p

Two dimensional molecular structure of the three anti-cancer drugs: midostaurin, enzastaurin and gefitinib.

<p>Two dimensional molecular structure of the three anti-cancer drugs: midostaurin, enzastaurin and gefitinib.</p

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></div

The predicted top upstream regulators in the comparison group female <i>vs</i>. male meningioma patients are tacrolimus, glutathione, ITPR, (E)-2,3',4,5'-tetramethoxystilbene, and SLC39A4 with a <i>p</i>-value of overlap of 1.16E-03, 1.55E-03, 2.02E-03, 2.02E-03, and 2.02E-03, respectively.

<p>Target genes are <i>APOD</i>, <i>KLRC4-KLRK1</i>/<i>KLRK1</i>, <i>MYH10</i>, <i>TNC</i>, <i>SLC7A11</i>, <i>CYP1B1</i>, and <i>NELL1</i>. Upregulated and downregulated genes in red and blue color, respectively. Asterisk indicates a gene that is represented in the dataset by more than one transcript.</p

Unsupervised hierarchical cluster analysis of 416 genes that were differentially expressed (<i>p</i>-value < 0.05; fold change > 2.0) between the three <i>DCC</i> expression groups.

<p>BN samples are included in cluster analysis. A number of genes is represented by more than one transcript. Meningiomas are clustering into two main branches, one of which contains the <i>DCC</i> low expression samples and a <i>DCC</i> medium expression sample that was a brain invasive case. Color scheme bar indicates comparably higher and lower expression values in red and blue color, respectively. Color scheme for samples: yellow, <i>DCC</i> low expression; green, <i>DCC</i> medium expression; orange, <i>DCC</i> high expression; BN samples, red.</p

The predicted top regulator effects network with a consistency score of 8.489 in the <i>DCC</i> low <i>vs</i>. <i>DCC</i> high expression comparison.

<p>Upstream regulators NFkB, PIK3R1, and CREBBP target a number of DEGs including <i>MMP2</i>, <i>SERPINE2</i>, <i>DOK5</i>, <i>SLC2A5</i>, <i>FST</i>, <i>TGM2</i>, <i>NR4A3</i>, <i>TGFB3</i>, <i>BCL2</i>, <i>NCAM1</i>, <i>TLR2</i>, <i>AR</i>, <i>CTGF</i>, <i>VEGFA</i>, <i>CYR61</i>, <i>VCAM1</i>, and <i>GDF15</i>. Connected downstream functions are entitled adhesion of leukemia cell lines, differentiation of cells, sprouting (including cell morphological characteristics), cell viability, and cell movement of phagocytes.</p