胃肠道肿瘤分子早诊

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Molecular Diagnosis of GI Cancer
胃肠道肿瘤分子诊断进展
卫生部国家临床重点专科
厦门大学附属中山医院消化内科
厦门大学消化疾病研究所
厦门市消化疾病中心
巴亚斯古楞
Summary, including clinically deployable markers and potential subtype-guided therapies for CRC
Part 1
Serum levels of TFF3 were significantly elevated
in both gastric and colorectal cancer patients
Urine levels of TFF3 were significantly elevated
in both gastric and colorectal cancer patients
Serum TFF3 levels as a prognostic marker for gastric cancer
Higher serum TFF3 level was significantly correlated
With the clinical stage (I-III vs IV) and distant metastasis
Serum levels as a prognostic marker for colorectal cancer
Higher serum TFF3 level
was significantly correlated
with the clinical stage (I-III
vs
IV)
and
distant
metastasis. Older patients
(age >60 y) were higher
than the levels of; different
numbers
of
lymphatic
metastases
Serum TFF3 levels as predictors of responses to
chemotherapy in gastric and colorectal cancer PR patients
Part 2
Serum level of JTB
*
ng/ml
P<0.0001
*
P<0.0001
Gastric
Colon
Healthy
cancer
cancer
individuals
Serum level of JTB
ng/ml
肠癌血清检测
JTB, how to become a biomarker?
Breakpoint
1q21
Chro 1
signal
Transmembrane
mJTB N
sJTB
C
N
ELISA
C
Digestive cancer patients
Blood samples
JTB逆转录示意图
确诊肿瘤病人外周血循环细
胞JTB-DNA-逆转录条带
阳性率统计结果
100%
75%
18%
JTB 条带位置的多样性,提示融合蛋白的存在
135KD
105KD
JTB
JTB
57KD
(Mybio)
(Novus)
48KD
38KD
15KD
tubulin
质谱鉴定结果
57KD Vimentin
38KD Unamed protein
48KD KRT8
融合基因鉴定
Hela
HepG2
750bp
RT-PCR
JTB-F
Vimentin-R
待测序报告?
Part 3
Microenvironments
Dev Cell. 2010 June 15; 18(6): 884–901
Nature Immunology 5, 88 - 97 : January 2004
The extracellular matrix protein mindin is a patternrecognition molecule for microbial pathogens
Department of Immunology, Duke University Medical Center, Durham,
Generation of Mindin-deficient mice
Table 1. Background of cancer patients and healthy
controls
Case No
Mindin (ng/mL)
P
Colorectal cancer
104
1.826±0.641
0.002
Esophageal cancer
25
2.446±0.604
0.031
Gastric cancer
39
2.007±0.100
0.008
Lung cancer
11
2.458±0.312
0.048
Breast cancer
5
1.677±0.249
0.044
Healthy control
96
3.746±0.617
--
Decreased serum Mindin levels can be used as a
biomarker for the early detection of colorectal cancer
Table 2. Clinicopathological characteristics of the colorectal
cancer group
Clinical features
Gender
Case No
Mindin (ng/mL)
Male
53
1.82±0.101
Female
51
1.966±0.118
Age
P
0.358
0.289
≤60
54
1.989±0.122
>60
50
1.818±0.102
Lesions
0.764
Colon
57
1.835±0.124
Rectum
47
1.904±0.121
Differentiation
0.057
Well-moderately
83
1.726±0.342
Poor
21
2.034±0.524
TNM staging
(I- II vs III- IV)
I
15
1.569±0.126
II
35
1.605±0.134
III
26
2.001±0.268
IV
28
2.278±0.274
0.017
ROC curve analysis
Mindin
had
76.15%
sensitivity
and
81.31%
specificity in separating
colorectal cancer patients
from the normal controls.
86.78% sensitivity and 81.25% specificity in
separating stage I-II patients and 51.85%
sensitivity and 80.21% specificity in
separating stage III-IV patients from the
healthy controls.
Mindin was significantly increased in the PR group after
chemotherapy, and its increase was identified as a
predictor for chemotherapy response in the PR group
Table 3. Patients with advanced colorectal cancer received
chemotherapy
Patient’s ID
Gender
Age
Mindin (ng/mL)
CEA (ng/mL)
CA199 (ng/mL)
CA125 (ng/mL)
TNM
Efficacy
Ⅰ-0
Male
54
1.283
4.6
20.4
10.5
TXN3M1
PR
Ⅰ-1
Male
54
11.128
3.8
18
8.1
TXN3M1
PR
Ⅰ-2
Male
54
10.187
4
18
8.1
TXN3M1
PR
Ⅱ-0
Male
58
3.261
1.2
6.8
9.2
T4N2M0
PD
Ⅱ-1
Male
58
3.045
1
6.5
8.7
T4N2M0
PD
Ⅱ-2
Male
58
3.054
1.3
7.5
8.9
T4N2M0
PD
Ⅲ-0
Female
46
3.616
1.9
13.9
13.1
T2N0M1
PR
Ⅲ-1
Female
46
3.726
2.2
15.8
14.9
T2N0M1
PR
Ⅲ-2
46
3.527
1.8
13
15.9
T2N0M1
PR
Ⅳ-0
Female
Male
68
0.531
1.3
30.2
74.2
T4aN3M1
SD
Ⅳ-1
Male
68
0.919
0.9
8.8
24
T4aN3M1
SD
Ⅳ-2
Male
68
5.027
1.3
5.9
26.1
T4aN3M1
SD
Ⅴ-0
Female
45
2.353
1
5.9
135
T3N2M1
PR
Ⅴ-1
Female
45
9.077
1.2
6.5
60.6
T3N2M1
PR
Ⅴ-2
45
10.025
1.6
5.8
30.1
T3N2M1
PR
Ⅵ-0
Female
Male
66
6.871
2
4.9
167
T4aN2aM1
SD
Ⅵ-1
Male
66
7.507
2.2
6.3
65.6
T4aN2aM1
SD
Ⅵ-2
Male
66
7.137
2.6
7.8
40.2
T4aN2aM1
SD
Ⅶ-0
Male
59
2.539
46.2
21.8
11.4
T4aN1M1
PR
Ⅶ-1
Male
59
2.491
117.5
297.2
16.4
T4aN1M1
PR
Ⅶ-2
Male
59
1.831
23.5
44.4
15.6
T4aN1M1
PR
Ⅷ-0
Male
62
1.962
10.8
0.6
111.1
TXN1M1
PR
Ⅷ-1
Male
62
1.788
4.8
0.6
42.1
TXN1M1
PR
Ⅷ-2
Male
62
1.706
6.7
1.3
38.5
TXN1M1
PR
Ⅸ-0
Male
52
3.114
16.7
350.8
6.3
T4N0M1
SD
Ⅸ-1
Male
52
3.223
12.2
270.9
6.9
T4N0M1
SD
Ⅸ-2
Male
52
3.018
8.2
234
5.9
T4N0M1
SD
Ⅹ-0
Male
73
2.114
4
10.4
7.5
T3N0M1
SD
Ⅹ-1
Male
73
2.681
3
10.8
6.7
T3N0M1
SD
Ⅹ-2
Male
73
4.049
3.3
10.5
8.3
T3N0M1
SD
Ⅺ-0
Female
56
1.4647
10.42
0.78
66.1
T3N2M1
SD
Ⅺ-1
Female
56
10.953
6.6
5.2
29.5
T3N2M1
SD
Ⅺ-2
56
10.512
3.0
4.3
17.6
T3N2M1
SD
Ⅻ-0
Female
Male
52
1.783
12.7
12.8
7.1
TXN0M1
SD
Ⅻ-1
Male
52
1.5
5.7
18
14.1
TXN0M1
SD
Ⅻ-2
Male
52
3.011
4
7.8
6.5
TXN0M1
SD
ⅩⅢ-0
Female
45
1.224
116.8
549.2
11
T4N2M1
PR
ⅩⅢ-1
ⅩⅢ-2
Female
Female
45
45
0.672
95.9
720.4
14.3
PR
10.635
25.9
220.4
14.3
T4N2M1
T4N2M1
PR
cancer
Mindin
promoter
EGR1 EGR1
cgcccccgc
Mindin
Expression
Results
Future plan
EGR1
Western
blot
CH-IP
报告基因
RT-PCR
组织中表达
Western
blot
Mindin
组织中表达
RT-PCR
Western blot
分子机制
信号通路
血清学检测
Our Goal
Combination of
TFF3, JTB and Mindin
for Early Diagnosis of GI
Cancer!
我力有限,靠你众力搏程;
我力有限,靠你定向领航;
遥遥苦辛路,浓浓同路情;
为了那一天,启程--
28
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