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Andrew D. Trister1,2, Brian Bot2, Andrea Hawkins-Daarud1, Kellie Fontes1, Carly Bridge1, Anne L. Baldock1, Jason K. Rockhill1, Maciej M. Mrugala1, Russ R. Rockne1, Erich Huang2, Kristin R. Swanson1
ˀ
1University of Washington, 2Sage BionetworksSeattle, WA
Measuring growth kinetics
A novel patient-specific model of glioma growth kinetics elucidates underlying biology as measured by gene expression microarray
Glioblastoma (GBM) is the most common primary brain tumor with universally poor prognosis. A hallmark of this disease is single-cell invasion into normal tissue. The kinetics of this invasion (D) and of cellular proliferation (ρ) can be estimated from routine pretreatment clinical imaging studies (MRI).
T1 + gad
T2 Distance
Glioma Cell Density
Distribution of kinetics
84 GBM patients with gene expression included in TCGA also had evaluable pretreatment MRI available for measurement.
100.5
101
101.5
102
102.5
103
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100.5 101 101.5 102 102.5
D (mm2/years)
rho
(1/y
ears
)
v = 9 mm/yr
v = 900 mm/yr
ρ/D
= 30
0 m
m2
ρ/D
= 0.
3 m
m2
SLOW
FAST
DIFFUSE
NODULAR
D (mm2/years)
ρ (1
/yea
rs)
Differential gene expression of GBM patients with varying growth kinetics
REMBRANDT includes gene expression microarray data from 475 patients with glioma (grades II-IV). Differential gene of GBM versus lower grade disease reveals 853 genes whose expression are specific for GBM.
9220853
2074
112464 13
4
Oligodendroglioma
Mixed gliomaAstro
cyto
ma
647 of these genes were also assessed in GBM patients in TCGA. Differential expression of 20 genes in a linear model of ρ are significant with an FDR < 0.05.
This work was funded in part by: Moffitt Cancer Center PSOC NIH/NCI U54CA143970Sage Bionetworks CCSB NIH/NCI U54CA149237
TCGA−02−0011−01B
TCGA−02−0024−01B
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TCGA−02−0021−01A
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TCGA−12−0773−01A
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TCGA−02−0055−01A
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TCGA−02−0051−01A
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TCGA−06−0206−01A
TCGA−26−5136−01B
TCGA−06−1087−01A
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TCGA−02−0009−01A
TCGA−26−5139−01A
TCGA−28−5215−01A
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TCGA−02−0025−01A
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TCGA−06−1800−01A
TCGA−19−2623−01A
TCGA−19−5947−01A
TCGA−06−0644−01A
TCGA−14−1396−01A
TCGA−06−0155−01B
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TCGA−14−0871−01A
TCGA−02−0057−01A
TCGA−12−0692−01A
TCGA−06−0147−01A
TCGA−28−1760−01A
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TCGA−02−0069−01A
TCGA−19−2624−01A
TCGA−08−0245−01A
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TCGA−14−3477−01A
TCGA−02−0014−01A
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TCGA−06−0195−01B
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TCGA−02−0016−01A
TCGA−02−2485−01A
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TCGA−14−0790−01B
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TCGA−06−0185−01A
TCGA−12−0670−01B
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TCGA−06−1804−01A
TCGA−27−1836−01A
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TCGA−28−5220−01A
TCGA−32−1970−01A
TCGA−06−2565−01A
TCGA−06−0126−01A
TCGA−06−0646−01A
TCGA−12−1599−01A
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TCGA−14−0812−01B
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TCGA−06−0744−01A
TCGA−06−0743−01A
TCGA−12−0819−01A
TCGA−27−1833−01A
TCGA−12−5295−01A
TCGA−76−4927−01A
TCGA−32−4719−01A
TCGA−32−2638−01A
TCGA−14−0786−01B
TCGA−41−2572−01A
TCGA−12−0703−01A
TCGA−12−3649−01A
TCGA−32−1978−01A
TCGA−19−2631−01A
TCGA−32−2632−01A
TCGA−76−4928−01B
TCGA−12−5299−01A
TCGA−02−2483−01A
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TCGA−26−5133−01A
TCGA−14−1821−01A
TCGA−16−0850−01A
TCGA−08−0344−01A
TCGA−06−2570−01A
TCGA−19−0960−01A
TCGA−06−0128−01A
TCGA−19−2629−01A
TCGA−32−1976−01A
TCGA−02−0074−01A
TCGA−27−2521−01A
TCGA−76−4925−01A
TCGA−06−5417−01A
TCGA−02−0003−01A
TCGA−02−0046−01A
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TCGA−19−0957−01C
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TCGA−08−0353−01A
TCGA−02−0026−01B
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TCGA−02−0048−01A
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TCGA−12−1088−01A
TCGA−28−2514−01A
TCGA−76−6192−01A
TCGA−14−0867−01A
TCGA−19−1392−01A
TCGA−41−3915−01A
TCGA−12−1099−01A
TCGA−06−0156−01A
TCGA−06−0188−01A
TCGA−12−1092−01B
TCGA−28−2502−01B
TCGA−06−0649−01B
TCGA−19−1387−01A
TCGA−16−0848−01A
TCGA−27−1830−01A
TCGA−08−0373−01A
TCGA−06−0240−01A
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TCGA−06−0167−01A
TCGA−28−2506−01A
TCGA−12−1098−01C
TCGA−06−0882−01A
TCGA−12−0822−01A
TCGA−06−0133−01A
TCGA−27−2526−01A
TCGA−14−1827−01A
TCGA−08−0244−01A
TCGA−26−1442−01A
TCGA−12−0818−01A
TCGA−28−1756−01C
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TCGA−19−1788−01A
TCGA−08−0351−01A
TCGA−06−6389−01A
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TCGA−02−0084−01A
TCGA−16−0849−01A
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TCGA−02−0080−01A
TCGA−14−1456−01C
TCGA−02−2486−01A
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TCGA−28−5204−01A
TCGA−06−0142−01A
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TCGA−19−2620−01A
TCGA−32−1980−01A
TCGA−02−0115−01A
TCGA−19−1388−01A
TCGA−28−1745−01B
TCGA−27−1834−01A
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TCGA−15−1446−01A
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TCGA−19−5952−01A
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TCGA−16−1047−01B
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TCGA−76−6193−01A
TCGA−32−4211−01A
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TCGA−19−5955−01A
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TCGA−19−1385−01A
TCGA−02−0034−01A
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TCGA−14−0789−01A
TCGA−28−2513−01A
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TCGA−02−0107−01A
TCGA−02−0064−01A
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TCGA−14−3476−01B
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TCGA−12−5301−01A
TCGA−02−0114−01A
TCGA−32−2634−01A
TCGA−76−6285−01A
TCGA−32−5222−01A
TCGA−06−5416−01A
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TCGA−41−2571−01A
TCGA−06−0875−01A
TCGA−14−1825−01A
TCGA−14−1454−01A
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TCGA−02−0033−01A
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TCGA−02−0083−01A
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TCGA−14−0865−01B
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TCGA−06−2567−01A
TCGA−32−2491−01A
TCGA−32−1987−01A
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TCGA−14−0817−01A
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TCGA−32−1979−01A
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TCGA−14−0783−01B
TCGA−08−0357−01A
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TCGA−32−1991−01A
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TCGA−27−1832−01A
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TCGA−19−2621−01B
TCGA−12−1090−01A
TCGA−14−1034−01A
TCGA−06−0879−01A
TCGA−32−4209−01A
TCGA−06−0145−01A
TCGA−08−0354−01A
TCGA−19−1791−01A
TCGA−12−0656−01B
TCGA−16−1045−01B
TCGA−06−2561−01A
TCGA−12−0826−01A
TCGA−27−1835−01A
TCGA−06−2564−01A
TCGA−19−5958−01A
TCGA−19−1386−01A
TCGA−06−2563−01A
TCGA−06−5414−01A
TCGA−28−5219−01A
TCGA−28−1757−01A
TCGA−19−1786−01A
TCGA−06−0157−01A
TCGA−02−0070−01A
TCGA−06−0750−01A
TCGA−32−1977−01A
TCGA−08−0356−01A
TCGA−02−0068−01A
TCGA−28−1755−01A
TCGA−28−1751−01A
TCGA−12−1094−01A
TCGA−26−1438−01A
TCGA−26−1440−01A
TCGA−16−1055−01B
TCGA−32−2494−01A
TCGA−76−4935−01A
TCGA−26−5135−01A
TCGA−14−1795−01A
TCGA−06−0745−01A
TCGA−27−2528−01A
TCGA−41−3393−01A
TCGA−06−1802−01A
TCGA−14−1794−01A
TCGA−12−0772−01A
TCGA−14−2555−01B
TCGA−06−0138−01A
TCGA−14−1459−01A
TCGA−14−1829−01A
TCGA−06−0197−01A
TCGA−02−0059−01A
TCGA−06−0201−01A
TCGA−02−2470−01A
TCGA−06−5412−01A
TCGA−06−0141−01A
TCGA−02−0089−01A
TCGA−14−2554−01A
TCGA−14−1823−01A
TCGA−06−0169−01A
TCGA−14−1402−01A
TCGA−06−0137−01A
TCGA−32−2495−01A
TCGA−08−0246−01A
TCGA−02−0023−01B
TCGA−06−0877−01A
TCGA−06−5418−01A
TCGA−76−4926−01B
TCGA−26−1443−01A
TCGA−19−0962−01B
TCGA−02−0039−01A
TCGA−27−2527−01A
TCGA−32−1982−01A
TCGA−41−4097−01A
TCGA−08−0352−01A
TCGA−14−0781−01B
TCGA−06−2562−01A
TCGA−19−2625−01A
TCGA−12−0778−01A
TCGA−06−0140−01A
TCGA−12−0707−01A
TCGA−19−0963−01B
TCGA−12−1093−01A
TCGA−14−0736−01A
TCGA−14−0813−01A
TCGA−08−0360−01A
TCGA−06−0645−01A
TCGA−02−0071−01A
TCGA−02−0085−01A
TCGA−12−0776−01A
TCGA−02−0099−01A
TCGA−19−1389−01A
TCGA−14−1037−01A
TCGA−12−0775−01A
2335_mt
10476_mt
8655_mt
55612_mt
8224_mt
5334_mt
6284_mt
5725_mt
25793_mt
800_mt
80723_mt
2997_mt
79801_mt
79719_mt
5373_mt
22974_mt
6241_mt
3488_mt
92689_mt
55076_mtTMEM45A
FAM114A1
IGFB5
RRM2
TPX2
PMM2
AAGAB
SHCBP1
GYS1
SLC35G2
CALD1
FBXO7
PTBP1
S100A13
PLCL1
SYN3
FERMT1
DYNLL1
ATP5H
FN1
Performing differential expression of these genes in a linear model with D demonstrated 37 genes with a significant FDR < 0.05
TCGA−26−5136−01B
TCGA−06−0130−01A
TCGA−02−0025−01A
TCGA−02−0028−01A
TCGA−02−0027−01A
TCGA−02−0057−01A
TCGA−02−0009−01A
TCGA−02−0043−01A
TCGA−06−1087−01A
TCGA−06−0206−01A
TCGA−06−0644−01A
TCGA−02−0004−01A
TCGA−02−0060−01A
TCGA−06−1800−01A
TCGA−06−0155−01B
TCGA−06−5858−01A
TCGA−28−1755−01A
TCGA−12−0692−01A
TCGA−12−0707−01A
TCGA−16−1062−01A
TCGA−16−1047−01B
TCGA−12−0829−01A
TCGA−06−0148−01A
TCGA−41−3915−01A
TCGA−02−0107−01A
TCGA−12−1092−01B
TCGA−08−0356−01A
TCGA−06−0125−01A
TCGA−06−2564−01A
TCGA−41−2572−01A
TCGA−19−5951−01A
TCGA−32−1977−01A
TCGA−16−1055−01B
TCGA−06−1802−01A
TCGA−14−0866−01B
TCGA−32−1982−01A
TCGA−06−1086−01A
TCGA−28−2514−01A
TCGA−12−0656−01B
TCGA−12−0703−01A
TCGA−06−0686−01A
TCGA−06−0745−01A
TCGA−16−1063−01B
TCGA−08−0358−01A
TCGA−06−0744−01A
TCGA−12−0820−01A
TCGA−06−1801−01A
TCGA−28−1753−01A
TCGA−76−6191−01A
TCGA−08−0353−01A
TCGA−28−1749−01A
TCGA−27−2528−01A
TCGA−27−1835−01A
TCGA−16−1056−01B
TCGA−16−0848−01A
TCGA−12−1600−01A
TCGA−19−1786−01A
TCGA−06−0157−01A
TCGA−19−0957−01C
TCGA−06−0126−01A
TCGA−06−0650−01A
TCGA−32−2494−01A
TCGA−76−4935−01A
TCGA−26−5135−01A
TCGA−02−0051−01A
TCGA−14−0736−01A
TCGA−02−0039−01A
TCGA−19−2625−01A
TCGA−06−0176−01A
TCGA−27−2527−01A
TCGA−32−4209−01A
TCGA−06−1084−01A
TCGA−06−0166−01A
TCGA−14−1402−01A
TCGA−14−1396−01A
TCGA−19−1790−01B
TCGA−08−0360−01A
TCGA−06−0124−01A
TCGA−19−5947−01A
TCGA−06−0139−01A
TCGA−06−0881−01A
TCGA−76−6193−01A
TCGA−76−6282−01A
TCGA−12−0778−01A
TCGA−26−1439−01A
TCGA−32−2638−01A
TCGA−19−5952−01A
TCGA−06−5410−01A
TCGA−06−5412−01A
TCGA−28−2502−01B
TCGA−02−0086−01A
TCGA−28−2513−01A
TCGA−27−2524−01A
TCGA−14−1452−01A
TCGA−28−1760−01A
TCGA−16−1060−01A
TCGA−02−0015−01A
TCGA−06−0154−01A
TCGA−06−0143−01A
TCGA−19−2619−01A
TCGA−32−4211−01A
TCGA−28−2501−01A
TCGA−06−0168−01A
TCGA−02−2470−01A
TCGA−12−1093−01A
TCGA−41−4097−01A
TCGA−19−0955−01A
TCGA−06−0141−01A
TCGA−12−1599−01A
TCGA−14−0789−01A
TCGA−06−0878−01A
TCGA−12−1088−01A
TCGA−26−1438−01A
TCGA−12−1096−01A
TCGA−16−1045−01B
TCGA−12−0776−01A
TCGA−19−5955−01A
TCGA−02−0068−01A
TCGA−27−1832−01A
TCGA−06−0122−01A
TCGA−28−1750−01A
TCGA−06−0156−01A
TCGA−02−0079−01A
TCGA−14−1034−01A
TCGA−14−1037−01A
TCGA−08−0346−01A
TCGA−06−0169−01A
TCGA−08−0345−01A
TCGA−14−1795−01A
TCGA−32−2491−01A
TCGA−87−5896−01A
TCGA−06−2562−01A
TCGA−41−3393−01A
TCGA−19−2623−01A
TCGA−76−4931−01A
TCGA−26−5132−01A
TCGA−32−1987−01A
TCGA−02−0075−01A
TCGA−06−0140−01A
TCGA−02−0070−01A
TCGA−27−1830−01A
TCGA−08−0373−01A
TCGA−08−0352−01A
TCGA−02−0102−01A
TCGA−76−4928−01B
TCGA−12−5299−01A
TCGA−28−5219−01A
TCGA−06−5414−01A
TCGA−02−0064−01A
TCGA−32−1986−01A
TCGA−14−0781−01B
TCGA−06−0192−01B
TCGA−28−1751−01A
TCGA−06−0645−01A
TCGA−12−1094−01A
TCGA−19−1389−01A
TCGA−12−0775−01A
TCGA−14−1794−01A
TCGA−19−1385−01A
TCGA−06−0147−01A
TCGA−12−0688−01A
TCGA−26−1443−01A
TCGA−12−0654−01B
TCGA−06−0750−01A
TCGA−12−0772−01A
TCGA−14−0867−01A
TCGA−12−0780−01A
TCGA−02−0071−01A
TCGA−06−0190−01A
TCGA−06−0211−01A
TCGA−02−0047−01A
TCGA−02−0007−01A
TCGA−06−5859−01A
TCGA−28−2506−01A
TCGA−06−0195−01B
TCGA−06−0240−01A
TCGA−19−1791−01A
TCGA−12−0670−01B
TCGA−06−0133−01A
TCGA−14−1827−01A
TCGA−12−1098−01C
TCGA−19−5960−01A
TCGA−06−1804−01A
TCGA−12−3646−01A
TCGA−06−0237−01A
TCGA−19−1789−01A
TCGA−12−0618−01A
TCGA−08−0359−01A
TCGA−28−5204−01A
TCGA−06−0167−01A
TCGA−06−0160−01A
TCGA−28−1756−01C
TCGA−19−1788−01A
TCGA−14−1458−01A
TCGA−12−0818−01A
TCGA−08−0344−01A
TCGA−16−0849−01A
TCGA−02−0080−01A
TCGA−14−1456−01C
TCGA−06−6389−01A
TCGA−02−0084−01A
TCGA−08−0351−01A
TCGA−15−1444−01A
TCGA−26−1442−01A
TCGA−06−0129−01A
TCGA−02−0014−01A
TCGA−14−4157−01A
TCGA−19−2629−01A
TCGA−12−3651−01A
TCGA−06−0142−01A
TCGA−02−0024−01B
TCGA−02−0011−01B
TCGA−02−0038−01A
TCGA−02−0116−01A
TCGA−02−0021−01A
TCGA−08−0392−01A
TCGA−06−2569−01A
TCGA−14−0871−01A
TCGA−32−1973−01A
TCGA−06−0188−01A
TCGA−06−6391−01A
TCGA−12−1099−01A
TCGA−16−1460−01A
TCGA−08−0350−01A
TCGA−12−0827−01A
TCGA−02−2466−01A
TCGA−19−2624−01A
TCGA−14−0865−01B
TCGA−14−1825−01A
TCGA−06−0875−01A
TCGA−14−1454−01A
TCGA−02−2483−01A
TCGA−76−4934−01A
TCGA−26−5134−01A
TCGA−06−1805−01A
TCGA−27−1836−01A
TCGA−28−1746−01A
TCGA−06−2558−01A
TCGA−14−1455−01A
TCGA−32−2634−01A
TCGA−06−0241−01A
TCGA−06−0174−01A
TCGA−02−0010−01A
TCGA−19−1390−01A
TCGA−02−0069−01A
TCGA−19−0960−01A
TCGA−02−0054−01A
TCGA−02−0058−01A
TCGA−06−2557−01A
TCGA−06−0238−01A
TCGA−06−2566−01A
TCGA−14−3477−01A
TCGA−41−2575−01A
TCGA−14−3476−01B
TCGA−06−0208−01A
TCGA−41−2571−01A
TCGA−41−2573−01A
TCGA−02−0104−01A
TCGA−06−0178−01A
TCGA−06−0221−01A
TCGA−12−1597−01B
TCGA−27−2521−01A
TCGA−06−5417−01A
TCGA−76−4925−01A
TCGA−02−0114−01A
TCGA−08−0385−01A
TCGA−02−0048−01A
TCGA−15−1449−01A
TCGA−15−1447−01A
TCGA−06−0128−01A
TCGA−76−4932−01A
TCGA−26−5133−01A
TCGA−16−0850−01A
TCGA−14−1821−01A
TCGA−02−0026−01B
TCGA−06−2570−01A
TCGA−28−5216−01A
TCGA−28−5209−01A
TCGA−28−5218−01A
TCGA−28−5215−01A
TCGA−26−5139−01A
TCGA−28−2509−01A
TCGA−08−0246−01A
TCGA−06−2561−01A
TCGA−12−3653−01A
TCGA−12−3650−01A
TCGA−06−0219−01A
TCGA−12−3644−01A
TCGA−12−3652−01A
TCGA−02−0083−01A
TCGA−12−5301−01A
TCGA−76−4929−01A
TCGA−14−2555−01B
TCGA−27−1831−01A
TCGA−06−0939−01A
TCGA−02−2486−01A
TCGA−14−1823−01A
TCGA−06−0197−01A
TCGA−06−0201−01A
TCGA−14−2554−01A
TCGA−32−2615−01A
TCGA−06−0187−01A
TCGA−06−0210−01A
TCGA−32−1991−01A
TCGA−06−5408−01A
TCGA−06−5418−01A
TCGA−76−4926−01B
TCGA−19−5950−01A
TCGA−27−2519−01A
TCGA−19−5959−01A
TCGA−16−1048−01B
TCGA−08−0347−01A
TCGA−08−0375−01A
TCGA−19−2631−01A
TCGA−06−0747−01A
TCGA−14−0787−01A
TCGA−08−0244−01A
TCGA−08−0354−01A
TCGA−08−0389−01A
TCGA−12−0616−01A
TCGA−08−0355−01A
TCGA−08−0390−01A
TCGA−06−0213−01A
TCGA−06−0876−01A
TCGA−12−0822−01A
TCGA−12−0828−01A
TCGA−02−0089−01A
TCGA−14−0783−01B
TCGA−14−0786−01B
TCGA−06−0184−01A
TCGA−28−6450−01A
TCGA−06−0145−01A
TCGA−06−5413−01A
TCGA−32−1978−01A
TCGA−06−2563−01A
TCGA−08−0357−01A
TCGA−27−2523−01A
TCGA−19−1386−01A
TCGA−15−0742−01A
TCGA−12−1095−01A
TCGA−14−1401−01A
TCGA−14−1451−01A
TCGA−06−0879−01A
TCGA−26−1440−01A
TCGA−06−0152−01A
TCGA−06−0137−01A
TCGA−12−0657−01A
TCGA−27−1838−01A
TCGA−02−0099−01A
TCGA−28−1757−01A
TCGA−12−0620−01A
TCGA−12−0619−01A
TCGA−02−0059−01A
TCGA−12−3648−01A
TCGA−06−0877−01A
TCGA−27−1837−01A
TCGA−19−5954−01A
TCGA−32−4213−01A
TCGA−06−2559−01A
TCGA−06−0646−01A
TCGA−32−1979−01A
TCGA−06−6390−01A
TCGA−19−1787−01B
TCGA−08−0386−01A
TCGA−41−5651−01A
TCGA−06−5411−01A
TCGA−28−2510−01A
TCGA−32−1980−01A
TCGA−32−4208−01A
TCGA−19−2620−01A
TCGA−06−0132−01A
TCGA−19−5958−01A
TCGA−06−5856−01A
TCGA−12−3649−01A
TCGA−12−0826−01A
TCGA−06−0173−01A
TCGA−06−0138−01A
TCGA−12−0821−01A
TCGA−06−0214−01A
TCGA−06−0158−01A
TCGA−26−1799−01A
TCGA−19−0963−01B
TCGA−12−1090−01A
TCGA−32−2616−01A
TCGA−12−0773−01A
TCGA−32−2498−01A
TCGA−08−0245−01A
TCGA−19−5956−01A
TCGA−32−5222−01A
TCGA−06−5416−01A
TCGA−28−5213−01A
TCGA−28−5214−01A
TCGA−28−5207−01A
TCGA−28−5208−01A
TCGA−02−0033−01A
TCGA−02−0046−01A
TCGA−02−0003−01A
TCGA−02−0052−01A
TCGA−02−0001−01C
TCGA−02−0055−01A
TCGA−02−0034−01A
TCGA−19−1388−01A
TCGA−28−1745−01B
TCGA−12−1089−01A
TCGA−15−1446−01A
TCGA−08−0380−01A
TCGA−32−4210−01A
TCGA−27−1834−01A
TCGA−28−1747−01C
TCGA−16−0846−01A
TCGA−06−0749−01A
TCGA−19−2621−01B
TCGA−27−1833−01A
TCGA−14−0790−01B
TCGA−14−1453−01A
TCGA−14−0817−01A
TCGA−12−5295−01A
TCGA−76−4927−01A
TCGA−02−0113−01A
TCGA−32−1970−01A
TCGA−12−0819−01A
TCGA−27−2518−01A
TCGA−06−0171−01A
TCGA−06−0216−01A
TCGA−06−0127−01A
TCGA−06−2565−01A
TCGA−12−1598−01A
TCGA−08−0349−01A
TCGA−02−0016−01A
TCGA−12−1097−01B
TCGA−06−0743−01A
TCGA−06−0648−01A
TCGA−08−0348−01A
TCGA−76−6285−01A
TCGA−19−4068−01A
TCGA−02−2485−01A
TCGA−06−0649−01B
TCGA−02−0085−01A
TCGA−14−0812−01B
TCGA−28−1752−01A
TCGA−02−0074−01A
TCGA−32−1976−01A
TCGA−12−1602−01A
TCGA−76−6192−01A
TCGA−32−2632−01A
TCGA−06−2567−01A
TCGA−19−1392−01A
TCGA−14−1459−01A
TCGA−27−2526−01A
TCGA−14−1829−01A
TCGA−02−0115−01A
TCGA−16−0861−01A
TCGA−19−0964−01A
TCGA−06−0882−01A
TCGA−81−5910−01A
TCGA−32−4719−01A
TCGA−41−3392−01A
TCGA−19−1387−01A
TCGA−14−0813−01A
TCGA−19−0962−01B
TCGA−12−1091−01A
TCGA−02−0023−01B
TCGA−32−2495−01A
TCGA−06−0185−01A
TCGA−28−5220−01A
TCGA−06−5415−01A
10633_mt26050_mt3745_mt11022_mt6579_mt8224_mt8398_mt54805_mt9472_mt56521_mt79754_mt65996_mt10766_mt55509_mt2615_mt57124_mt56901_mt49855_mt29015_mt2335_mt8655_mt5806_mt157567_mt80723_mt7050_mt79143_mt4162_mt4601_mt10135_mt715_mt5420_mt800_mt23333_mt84617_mt4478_mt1284_mt1282_mtCOL4A1
COL4A2MSNTUBB6DPY19L1CALD1PODXLC1RNAMPTMXI1MCAMMBOAT7TGIF1SLC35G2ANKRD46PTXDYNLL1FN1SLC43A3SCAPERNDUFA4L2CD248LRRC32BATF3TOB2MGC2752ASB13DNAJC12AKAP6CNNM2PLA2G6SYN3SLCO1A2TDRKHKCNB1SLITRK5RASL10A
84 subjects
84 subjects
Gene set enrichment analysis with gene lists derived from the differential gene expression calculation revealed:
High D tumors are enriched for gene expression related to cell migration, integrin interactions and HIF activation with a relative reduction in genes related to focal-adhesions and extracellular matrix maintenance
High ρ tumors are enriched for genes related to resistance to therapy, induction after ionizing radiation and HIF pathway knock-down
This work demonstrates the potential to assess underlying differences in biology in a heterogeneous disease from measurements of routine clinical imaging. We have previously shown that patients with high ρ tumors have worse survival, and here we find that these patients also differentially express genes related to treatment resistance and response to radiation. We have also found that patients with high D tumors demonstrate a decrease in gene expression related to focal adhesion and increase in motility genes.
Future work will validate these findings in external datasets and in biological specimens.
Survival based on gene set
Gene set enrichment analysis
0.0
0.2
0.4
0.6
0.8
1.0
p = 0.000222
stratabigClust$class=1bigClust$class=2
Building a classifier from these genes on 466 GBM patients in TCGA reveals two classes of patients with significantly different survival probability.
Conclusions
0.00.2
0.40.6
0.81.0
−1.0 −0.5 0.0 0.5 1.0
7
13
11
12
8
9
0.00.2
0.40.6
0.81.0
−1.0 −0.5 0.0 0.5 1.0
7
13
10
11
12
8
9
References: 1CH Wang, JK Rockhill, M Mrugala, et al. Cancer Res 2009;69:9133-9140 2M Szeto, G Chakraborty, J Hadley, et al. Cancer Res 2009;69:4502-4509
p=0.000222
10
Log
2 ex
pres
sion
Log
2 ex
pres
sion
1.0
0.8
0.6
0.4
0.2
0
0 1 2 3 4 5 6 7 8 9 10
Survi
val p
roba
bility
Time (years)