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

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

Gastric

cancer

Colon

cancer

Healthy

individuals

ng

/ml

Serum level of JTB

*

*P<0.0001

P<0.0001

Part 2

ng

/ml

Serum level of JTB

肠癌血清检测

JTB, how to become a biomarker?

mJTB

sJTB

signal Transmembrane

N C

ELISA

Digestive cancer patients Blood samples

N C

1q21

Breakpoint

Chro 1

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

100%

Tum

or

Health

75%

18%

阳性率统计结果

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

57KD Vimentin

48KD KRT8

38KD Unamed protein

质谱鉴定结果

JTB-F Vimentin-R

融合基因鉴定

RT-PCR

750bp

Hela HepG2

待测序报告？

Dev Cell. 2010 June 15; 18(6): 884–901

Microenvironments

Part 3

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

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 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

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

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

EGR1

MindinExpression

MindinExpressionEGR1

cgcccccgc

cancer

Mindin promoter

Results

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

Combination of TFF3, JTB and Mindin

for Early Diagnosis of GI Cancer!

Our Goal

28

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