Expression and Significance of E-cadherin， MMP-2 Protein， and MMP-9 Protein in Gastric Cancer Tissues_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

FENG Ning ¹ ,  WU Xiaoting ² , GAO Haide ¹ , LIU Wenzhi ¹ , Chen Xi ¹

1.Department of General Surgery， Affiliated Zhongshan Hospital of Dalian University， Dalian 116001， Liaoning Province， China;;
2.Department of Gastrointestinal Surgery， West China Hospital， Sichuan University， Chengdu 610041， Sichuan Province， China;

Corresponding author：

WU Xiaoting, Email: wxt1@medmail.com.cn

Keywords：

E-cadherin; Matrix metalloproteinases-2; Matrix metalloproteinases-9; Gastric cancer

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective 　To explore the expressions of E-cadherin， matrix metalloproteinases-2 （MMP-2） protein，and matrix metalloproteinases-9 （MMP-9） protein in gastric cancer tissues， and to analyze the possible statistical relati-
onship between the expressions of E-cadherin， MMP-2 protein， and MMP-9 protein， and clinicopathological features of
gastric cancer.
Methods 　The ABC immunohistochemical staining was adopted to examine the expressions of E-cadherin，
MMP-2 protein， and MMP-9 protein in 40 paraffin slices of gastric cancer （gastric cancer group）， with the adjacent tissue as the control group （adjacent tissue group）. The positive rates of 3 kinds of protein were compared between the
2 groups， in addition， the statistical relationship between the expressions of the 3 kinds of protein and clinicopathological features of gastric cancer was examined respectively by SPSS 19.0 software.
Results 　The expressions of E-cadherin， MMP-2 protein， and MMP-9 protein were all found in gastric cancer tissues and adjacent tissues. In gastric cancer tissue group， the expression of E-cadherin downregulated while the expressions of MMP-2 protein and MMP-9 protein upregulated in comparison to adjacent tissue group （P＜0.05）. The significant association was found between the expre-ssion of E-cadherin and the gastric cancer tissues of T3＋T4 stage， N1-N3 stage， and Ⅲ＋Ⅳ stage， which had lower positive expression rate （P＜0.05）. The expression of MMP-2 protein in gastric cancer tissues of M1 stage and Ⅲ＋Ⅳstage upregulated （P＜0.05）， and the expression of MMP-9 protein upregulated in gastric cancer tissues of T3＋T4 stage，Ⅲ＋Ⅳ stage， or lowlydifferentiated＋undifferentiated （P＜0.05）. No significant relationship was found in other clinical-
pathological features and 3 kinds of protein except aforementioned significant relationship （P＞0.05）.
Conclusions 　In the development progress of gastric cancer， the E-cadherin may get involved in the mechanism of tumor invasion and lymph node metastasis， MMP-2 protein may get involved in the mechanism of distant metastasis， and MMP-9 protein may get involved in the mechanism of differentiation and tumor invasion. The examination of those 3 kinds of markers may play an role in the judgment of tumor stage and estimation of prognosis in gastric cancer clinically.

Citation： FENG Ning,WU Xiaoting,GAO Haide,LIU Wenzhi,Chen Xi. Expression and Significance of E-cadherin， MMP-2 Protein， and MMP-9 Protein in Gastric Cancer Tissues. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2013, 20(12): 1401-1406. doi: Copy

1.	Zazula M， Ferreira AM， Czopek JP， et al. CDH1 gene promoterhypermethylation in gastric cancer：relationship to Goseki grading，microsatellite instability status， and EBV invasion[J]. Diagn Mol Pathol， 2006， 15(1)：24-29.
2.	Graziano F， Arduini F， Ruzzo A， et al. Combined analysis ofE-cadherin gene (CDH1) promoter hypermethylation and E-cad-herin protein expression in patients with gastric cancer：implications for treatment with demethylating drugs[J]. Ann Oncol， 2004， 15(3)：489-492.
3.	Shim KN， Jung SA， Joo YH， et al. Clinical significance of tissuelevels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in gastric cancer[J]. J Gastroenterol， 2007， 42(2)：120-128.
4.	中华人民共和国卫生部医政司. 胃癌诊疗规范(2011年版)[J]. 中国医学前沿杂志：电子版， 2012， 4(5)：62-71.
5.	Sampieri CL， León-Córdoba K， Remes-Troche JM. Matrix meta-lloproteinases and their tissue inhibitors in gastric cancer as mole-cular markers[J]. J Cancer Res Ther， 2013， 9(3)：356-363.
6.	王鹏，郭琳，王强. PTEN、Fas/FasL和MMP-2在胃癌组织的表达及其临床意义[J]. 中国普外基础与临床杂志， 2009， 16(12)：991-995.
7.	Song SY， Kim S， Kim DS， et al. Abnormal expression of E-cad-herin in early gastric carcinoma：its relationship with macroscopic growth patterns and catenin alpha and beta[J]. J Clin Gastroenterol， 2004， 38(3)：252-259.
8.	Blok P， Craanen ME， Dekker W， et al. Loss of E-cadherin expression in early gastric cancer[J]. Histopathology， 1999， 34(5)：410-415.
9.	Ohene-Abuakwa Y， Noda M， Perenyi M， et al. Expression of the E-cadherin/catenin (alpha-， beta-， and gamma-) complex corre-lates with the macroscopic appearance of early gastric cancer[J]. J Pathol， 2000， 192(4)：433-439.
10.	Joo YE， Rew JS， Choi SK， et al. Expression of e-cadherin and catenins in early gastric cancer[J]. J Clin Gastroenterol， 2002， 35(1)：35-42.
11.	Liu XJ， Chen ZF， Li HL， et al. Interaction between cyclooxygenase-2， Snail， and E-cadherin in gastric cancer cells[J]. World J Gastroenterol， 2013， 19(37)：6265-6271.
12.	Wang ZS， Shen Y， Li X， et al. Significance and prognostic value of Gli-1 and Snail/E-cadherin expression in progressive gastric cancer[J]. Tumour Biol， 2013. [Epub ahead of print].
13.	Moghbeli M， Moaven O， Memar B， et al. Role of hMLH1 and E-cadherin promoter methylation in gastric cancer progression[J]. J Gastrointest Cancer， 2013. [Epub ahead of print].
14.	Chen Z， Liu M， Liu X， et al. COX-2 regulates E-cadherin expr-ession through the NF-κB/Snail signaling pathway in gastric cancer[J]. Int J Mol Med， 2013， 32(1)：93-100.
15.	Li X， Gao Y， Pan Y， et al. Mutation screen and RNA analysis disclose the changed splicing of the E-cadherin transcription in gastric cancer[J]. Fam Cancer， 2013， 12(3)：547-554.
16.	Corso G， Carvalho J， Marrelli D， et al. Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer[J]. J Clin Oncol， 2013， 31(7)：868-875.
17.	Kim S， Chung JW， Jeong TD， et al. Searching for E-cadherin gene mutations in early onset diffuse gastric cancer and hereditarydiffuse gastric cancer in Korean patients[J]. Fam Cancer， 2013，12(3)：503-507.
18.	Hu Z， Liu X， Tang Z， et al. Possible regulatory role of Snail in NF-κB-mediated changes in E-cadherin in gastric cancer[J]. Oncol Rep， 2013， 29(3)：993-1000.
19.	Xing X， Tang YB， Yuan G， et al. The prognostic value of E-cad-herin in gastric cancer：a meta-analysis[J]. Int J Cancer， 2013， 132(11)：2589-2596.
20.	Pinheiro H， Carvalho J， Oliveira P， et al. Transcription initiation arising from E-cadherin/CDH1 intron2：a novel protein isoform that increases gastric cancer cell invasion and angiogenesis[J]. Hum Mol Genet， 2012， 21(19)：4253-4269.
21.	陈振栋，吉志武，安树才，等. HIF-1α和MMP-2在低分化胃癌中的表达及与浸润转移的关系[J]. 中国普外基础与临床杂志， 2010， 17(2)：187-188.
22.	Holmberg C， Ghesquière B， Impens F， et al. Mapping proteol-ytic processing in the secretome of gastric cancer-associated myofi-broblasts reveals activation of MMP-1， MMP-2， and MMP-3[J].J Proteome Res， 2013， 12(7)：3413-3422.
23.	Liu HQ， Song S， Wang JH， et al. Expression of MMP-3 and TIMP-3 in gastric cancer tissue and its clinical significance[J]. Oncol Lett， 2011， 2(6)：1319-1322.
24.	Dong Z， Xu X， Du L， et al. Leptin-mediated regulation of MT1-MMP localization is KIF1B dependent and enhances gastric cancer cell invasion[J]. Carcinogenesis， 2013， 34(5)：974-983.
25.	Wu T， Li Y， Lu J， et al. Increased MMP-21 expression is associated with poor overall survival of patients with gastric cancer[J]. Med Oncol， 2013， 30(1)：323.

1. Zazula M， Ferreira AM， Czopek JP， et al. CDH1 gene promoterhypermethylation in gastric cancer：relationship to Goseki grading，microsatellite instability status， and EBV invasion[J]. Diagn Mol Pathol， 2006， 15(1)：24-29.
2. Graziano F， Arduini F， Ruzzo A， et al. Combined analysis ofE-cadherin gene (CDH1) promoter hypermethylation and E-cad-herin protein expression in patients with gastric cancer：implications for treatment with demethylating drugs[J]. Ann Oncol， 2004， 15(3)：489-492.
3. Shim KN， Jung SA， Joo YH， et al. Clinical significance of tissuelevels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in gastric cancer[J]. J Gastroenterol， 2007， 42(2)：120-128.
4. 中华人民共和国卫生部医政司. 胃癌诊疗规范(2011年版)[J]. 中国医学前沿杂志：电子版， 2012， 4(5)：62-71.
5. Sampieri CL， León-Córdoba K， Remes-Troche JM. Matrix meta-lloproteinases and their tissue inhibitors in gastric cancer as mole-cular markers[J]. J Cancer Res Ther， 2013， 9(3)：356-363.
6. 王鹏，郭琳，王强. PTEN、Fas/FasL和MMP-2在胃癌组织的表达及其临床意义[J]. 中国普外基础与临床杂志， 2009， 16(12)：991-995.
7. Song SY， Kim S， Kim DS， et al. Abnormal expression of E-cad-herin in early gastric carcinoma：its relationship with macroscopic growth patterns and catenin alpha and beta[J]. J Clin Gastroenterol， 2004， 38(3)：252-259.
8. Blok P， Craanen ME， Dekker W， et al. Loss of E-cadherin expression in early gastric cancer[J]. Histopathology， 1999， 34(5)：410-415.
9. Ohene-Abuakwa Y， Noda M， Perenyi M， et al. Expression of the E-cadherin/catenin (alpha-， beta-， and gamma-) complex corre-lates with the macroscopic appearance of early gastric cancer[J]. J Pathol， 2000， 192(4)：433-439.
10. Joo YE， Rew JS， Choi SK， et al. Expression of e-cadherin and catenins in early gastric cancer[J]. J Clin Gastroenterol， 2002， 35(1)：35-42.
11. Liu XJ， Chen ZF， Li HL， et al. Interaction between cyclooxygenase-2， Snail， and E-cadherin in gastric cancer cells[J]. World J Gastroenterol， 2013， 19(37)：6265-6271.
12. Wang ZS， Shen Y， Li X， et al. Significance and prognostic value of Gli-1 and Snail/E-cadherin expression in progressive gastric cancer[J]. Tumour Biol， 2013. [Epub ahead of print].
13. Moghbeli M， Moaven O， Memar B， et al. Role of hMLH1 and E-cadherin promoter methylation in gastric cancer progression[J]. J Gastrointest Cancer， 2013. [Epub ahead of print].
14. Chen Z， Liu M， Liu X， et al. COX-2 regulates E-cadherin expr-ession through the NF-κB/Snail signaling pathway in gastric cancer[J]. Int J Mol Med， 2013， 32(1)：93-100.
15. Li X， Gao Y， Pan Y， et al. Mutation screen and RNA analysis disclose the changed splicing of the E-cadherin transcription in gastric cancer[J]. Fam Cancer， 2013， 12(3)：547-554.
16. Corso G， Carvalho J， Marrelli D， et al. Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer[J]. J Clin Oncol， 2013， 31(7)：868-875.
17. Kim S， Chung JW， Jeong TD， et al. Searching for E-cadherin gene mutations in early onset diffuse gastric cancer and hereditarydiffuse gastric cancer in Korean patients[J]. Fam Cancer， 2013，12(3)：503-507.
18. Hu Z， Liu X， Tang Z， et al. Possible regulatory role of Snail in NF-κB-mediated changes in E-cadherin in gastric cancer[J]. Oncol Rep， 2013， 29(3)：993-1000.
19. Xing X， Tang YB， Yuan G， et al. The prognostic value of E-cad-herin in gastric cancer：a meta-analysis[J]. Int J Cancer， 2013， 132(11)：2589-2596.
20. Pinheiro H， Carvalho J， Oliveira P， et al. Transcription initiation arising from E-cadherin/CDH1 intron2：a novel protein isoform that increases gastric cancer cell invasion and angiogenesis[J]. Hum Mol Genet， 2012， 21(19)：4253-4269.
21. 陈振栋，吉志武，安树才，等. HIF-1α和MMP-2在低分化胃癌中的表达及与浸润转移的关系[J]. 中国普外基础与临床杂志， 2010， 17(2)：187-188.
22. Holmberg C， Ghesquière B， Impens F， et al. Mapping proteol-ytic processing in the secretome of gastric cancer-associated myofi-broblasts reveals activation of MMP-1， MMP-2， and MMP-3[J].J Proteome Res， 2013， 12(7)：3413-3422.
23. Liu HQ， Song S， Wang JH， et al. Expression of MMP-3 and TIMP-3 in gastric cancer tissue and its clinical significance[J]. Oncol Lett， 2011， 2(6)：1319-1322.
24. Dong Z， Xu X， Du L， et al. Leptin-mediated regulation of MT1-MMP localization is KIF1B dependent and enhances gastric cancer cell invasion[J]. Carcinogenesis， 2013， 34(5)：974-983.
25. Wu T， Li Y， Lu J， et al. Increased MMP-21 expression is associated with poor overall survival of patients with gastric cancer[J]. Med Oncol， 2013， 30(1)：323.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression and Significance of E-cadherin， MMP-2 Protein， and MMP-9 Protein in Gastric Cancer Tissues

Abstract Full text Figures/Tables Video References Cited by

Format

Content