Molecular Diagnosis of GI Cancer 胃肠道肿瘤分子诊断进展
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Transcript of Molecular Diagnosis of GI Cancer 胃肠道肿瘤分子诊断进展
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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附属中山医院消化内科厦门大学消化疾病研究所厦门大学消化疾病研究所厦门市消化疾病中心厦门市消化疾病中心
巴亚斯古楞巴亚斯古楞
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Summary, including clinically deployable markers and potential subtype-guided therapies for CRC
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Part 1
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Serum levels of TFF3 were significantly elevated in both gastric and colorectal cancer patients
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Urine levels of TFF3 were significantly elevated in both gastric and colorectal cancer patients
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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
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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
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Serum TFF3 levels as predictors of responses to chemotherapy in gastric and colorectal cancer PR patients
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Gastric
cancer
Colon
cancer
Healthy
individuals
ng
/ml
Serum level of JTB
*
*P<0.0001
P<0.0001
Part 2
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ng
/ml
Serum level of JTB
肠癌血清检测
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JTB, how to become a biomarker?
mJTB
sJTB
signal Transmembrane
N C
ELISA
Digestive cancer patients Blood samples
N C
1q21
Breakpoint
Chro 1
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JTB逆转录示意图
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确诊肿瘤病人外周血循环细胞 JTB-DNA-逆转录条带
100%
Tum
or
Health
75%
18%
阳性率统计结果
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135KD105KD
57KD
48KD
38KD
15KD
tubulin
Hela-
pu6
Hel
a-si
JTB
Hela-
pu6
Hel
a-si
JTB
Hela-
pu6
Hel
a-si
JTB
Hela-
pu6
JTB(Mybio)
JTB(Novus)
JTB 条带位置的多样性,提示融合蛋白的存在
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57KD Vimentin
48KD KRT8
38KD Unamed protein
质谱鉴定结果
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JTB-F Vimentin-R
融合基因鉴定
RT-PCR
750bp
Hela HepG2
待测序报告?
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Dev Cell. 2010 June 15; 18(6): 884–901
Microenvironments
Part 3
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Nature Immunology 5, 88 - 97 : January 2004
The extracellular matrix protein mindin is a pattern-recognition molecule for microbial pathogens
Department of Immunology, Duke University Medical Center, Durham,
Generation of Mindin-deficient mice
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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 --
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Decreased serum Mindin levels can be used as a biomarker for the early detection of colorectal cancer
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Table 2. Clinicopathological characteristics of the colorectal cancer group
Clinical features Case No Mindin (ng/mL) PGender 0.358
Male 53 1.82±0.101
Female 51 1.966±0.118
Age 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) 0.017
I 15 1.569±0.126
II 35 1.605±0.134
III 26 2.001±0.268
IV 28 2.278±0.274
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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.
ROC curve analysis
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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 chemotherapyPatient’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 Female 46 3.527 1.8 13 15.9 T2N0M1 PR
Ⅳ-0 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 Female 45 10.025 1.6 5.8 30.1 T3N2M1 PR
Ⅵ-0 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 Female 56 10.512 3.0 4.3 17.6 T3N2M1 SD
Ⅻ-0 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 Female 45 0.672 95.9 720.4 14.3 T4N2M1 PR
ⅩⅢ-2 Female 45 10.635 25.9 220.4 14.3 T4N2M1 PR
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EGR1
MindinExpression
MindinExpressionEGR1
cgcccccgc
cancer
Mindin promoter
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Results
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Future plan
分子机制信号通路
Mindin
Western blot
Western blot
血清学检测
RT-PCR
报告基因
EGR1
组织中表达
CH-IP
Western blot
RT-PCR组织中表达
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Combination of TFF3, JTB and Mindin
for Early Diagnosis of GI Cancer!
Our Goal
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