Original Article Non-invasive longitudinal imaging of tumor progression using an 111indium
Early Adenoma Normal Hyperplasti c Dysplastic Carcinoma Polyp Metastasis (to Liver) COLON CANCER -...
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Transcript of Early Adenoma Normal Hyperplasti c Dysplastic Carcinoma Polyp Metastasis (to Liver) COLON CANCER -...
Early
AdenomaNormal Hyperplasti
c
Dysplastic
Carcinoma Polyp Metastasis
(to Liver)
COLON CANCER - TUMOR PROGRESSION:
Tumor progression
22 Normal colon
24 polyp
47 primary cancer
19 lung metastasis
16 liver metastasis
5 normal lung
11 normal liver
First stage: Total of 144 micro-dissected samples Performed on Affymetrix GeneChip U133A (22,283 probe-sets)
Colon cancer - global view
Expression 1-99%
20 40 60 80 100 120 140
100
200
300
400
500
600
700
800
900
1000
22 Normal colon
24 polyp
47 primary cancer
19 lung metastasis
16 liver metastasis
5 normal lung
11 normal liver
First stage: Total of 144 micro-dissected samples Performed on Affymetrix GeneChip U133A (22,283 probe-sets)
1st PCA: tissue2nd PCA: transformation3rd PCA: muscle/connective contamination2 of the dominant signals are not relevant
Colon cancer – PCA
SPIN: MOTIVATION
GLOBAL LAYOUT OF DATA
IDENTIFY RELEVANT SUBSETS OF GENES
SHAPES OF DATA “CLOUDS”
DEMONSTRATE ON COLONCANCER DATA
Expression 1-99%
20 40 60 80 100 120 140
100
200
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400
500
600
700
800
900
1000
SORTINGExpression 1-99%
A
B
H
K
M
U
V
100
200
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500
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700
800
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1000
livermetlungmetcolonpolypcarc.
4 points
Gene 1
Gen
e 2expression levels of 2 genes
for 4 patients:
(5) (19) (27) (37)
1 9 11 3 8 2 4 6
Gene 1
Gene 2
4 POINTS IN 2-DIMENSIONS:
(27)
(19)
22 Normal colon
24 polyp
47 primary cancer
19 lung metastasis
16 liver metastasis
5 normal lung
11 normal liver
First stage: Total of 144 micro-dissected samples Performed on Affymetrix GeneChip U133A (22,283 probe-sets)
1st PCA: tissue2nd PCA: transformation3rd PCA: muscle/connective contamination2 of the dominant signals are not relevant
Colon cancer – PCA
45 samples
17,3
00 p
robe
s
-30
-20
-10
0
10
-10
0
10
20
-15
-10
-5
0
5
10
15
20
25
a8b a8o
PCA 2 PCA 1
e8b a8b
a8g a8+
a8g
a6o e6b a6g a8b
a6g
e6b e6b
e8g
e6g
e6b
e8b e6b
e6b
e8g
e8b e8b
e6g
e6g
e6g e6g
e6b e6b
c8o
e8g
e3b c8o
e6g
a6g
e6+
e9o c6o
c8o
c6o
noo
PC
A 3
noo
noo noo
noo
PCA 1PCA 2
PC
A 3
Cervical Cancer - Gene Expression Matrix
5 Normal cervical tissues35 Tumors (5 repeats) 5 Cancer cell lines
Focus on relevant samples
-15-10
-50
510
15-10
-5
0
5
10
15-10
-5
0
5
10
e6g a8b
e8b
a8b
PCA 1
PCA 2
e6b
a8o
e6+
a8g
a6g
e6b
e6g
e8b
e6b
e8g e6b
e8g
e6g
a8b e8g
e6g
e6b
e3b
e9o
a6g
a6o
a8+
e8b
e6b e6g
PC
A 3
PCA 2PCA 1
PC
A 3
Removed the cell lines, the normals, the a6g (29-3) that clustered with the normals; kept 1 of each repeat29 samples
17,3
00 p
robe
s
toy distmat
0.0 10.0 10.77 2.8210.0 0.0 2.82 7.2110.77 2.82 0.0 8.242.82 7.21 8.24 0.0
0.0 2.82 10.0 10.77 10.0 7.21 0.0 2.82
10.77 8.24 2.82 0.0 2.82 0.0 7.21
8.24 0.0 2.82 10.0 10.77
2.82 0.0 7.21 8.24 10.0 7.21 0.0 2.82
10.77 8.24 2.82 0.0
(5) (19) (27) (37)
toy distmat ordered
0.0 10.0 10.77 2.8210.0 0.0 2.82 7.2110.77 2.82 0.0 8.242.82 7.21 8.24 0.0
0.0 2.82 10.0 10.77 2.82 0.0 7.21 8.24
10.0 7.21 0.0 2.82 10.77 8.24 2.82 0.0
(5) (19) (27) (37) (5) (37) (19) (27)
17 Primary GlioBlastoMa3 Cell Lines
1185 Genes, 36 Samples
GLIOBLASTOMA:
glioblastoma
CLONTECH ARRAYS
S Godard, G Getz, H Kobayashi, P Farmer, M Delorenzi, M Nozaki, A-C Diserens, M-F Hamou, P-Y Dietrich, J-G Villemure, R C. Janzer,
P Bucher, R Stupp, N de Tribolet, E Domany, M E. Hegi
12 Astrocytoma(II) 4 secondary GBM
174 genes separate (at FDR of 5%) PrGBM from LGA + ScGBM
-3
-2
-1
0
1
2
3
4
5 10 15 20 25 30
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