Epithelial-Mesenchymal Transition Related Factors and CD133 Protein Expressions in Primary Lesion of Gastric Cancer and Its Relationship with Clinicopathologic Features and Prognosis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

CAI Cheng , YU Jiwei , WU Jugang , LU Ruiqi , NI Xiaochun , WANG Shoulian ,  JIANG Bojian

The First Department of General Surgery， No. 3 People’s Hospital， Shanghai Jiao-Tong University School of Medicine， Shanghai 201900， China;

Corresponding author：

JIANG Bojian, Email: jiang_md@hotmail.com

Keywords：

Stomach; Carcinoma/Neoplasma; Epithelial-mesenchymal transition; CD133; Prognosis; Western blot method

Video：

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Objective 　To investigate the prognostic value of epithelial-mesenchymal transition （EMT） related proteins （Snail， E-cadherin， and N-cadherin） in gastric cancer and its relationship with tumor initiating cells （TICs） marker （CD133）.
Methods 　The expressions of EMT-related proteins and CD133 protein in the gastric cancer tissues and normal gastric mucosa tissues adjacent to gastric cancer were detected by Western blot method. The relations between the expressions of EMT-related factors proteins and CD133 protein and the clinicopathologic characters were analyzed. The correlations between EMT-related factors and CD133 were analyzed by Spearman. The correlations between EMT-related factors expressions and CD133 expression and survival were analyzed by Kaplan-Meier method and Log-rank test.
Results 　① The protein expression levels of Snail， N-cadherin， and CD133 in the gastric cancer tissues were significantly higher than those in the normal gastric mucosa tissues adjacent to gastric cancer （Snail：0.599±0.114 versus 0.259±0.108， P=0.020；N-cadherin：0.754±0.154 versus 0.329±0.134， P=0.001；CD133：0.635±0.119 versus 0.485±0.116， P=0.029）， while the protein expression level of E-cadherin was lower than that in the normal gastric mucosa tissues adjacent to gastric cancer （0.378±0.123 versus 0.752±0.156， P=0.003）.② The expression levels of Snail and N-cadherin in the gastric cancer patients with vascular invasion， lymphatic vessel invasion，N3 lymph node metastasis， diameter more than 5 cm， and Ⅲ＋Ⅳ staging were significantly higher than those in the patients without vascular invasion， lymphatic vessel invasion， N0-N2 lymph node metastasis， diameter less than 5 cm， andⅠ＋Ⅱ staging（P＜0.05）， while E-cadherin protein expression was lower than that in the patients without vascular invasion， lymphatic vessel invasion， N0-N2 lymph nodes metastasis， andⅠ＋Ⅱstaging （P＜0.05）. The expression levels of CD133 in the gastric cancer patients with lymphatic vessel invasion， diameter more than 5 cm， and Ⅲ＋Ⅳ staging were significantly higher than those in the patients without lymphatic vessel invasion， diameter less than 5 cm， andⅠ＋Ⅱ staging （P＜0.05）. ③The Snail and N-cadherin protein expressions were significantly positive correlated with CD133 protein expression， respectively （rs=0.278， P=0.048；rs=0.406， P=0.003）， while E-cadherin protein expression was significantly negative correlated with CD133 protein expression （rs=-0.504， P=0.000）.④ The survival time in the patients with lower expressions of Snail， N-cadherin， and CD133 were significantly longer than those in the patients with higher expressions of Snail， N-cadherin， and CD133 （P＜0.05）. The combination of Snail， N-cadherin， E-cadherin， and CD133 could effectively predict survival.
Conclusions 　There is a significant correlation between EMT and gastric cancer TICs， and which are correlated with aggressive clinicopathologic features of gastric cancer. The combination of Snail， E-cadherin， N-cadherin， and CD133 may be effectively predict the prognosis of gastric cancer patients.

Citation： CAI Cheng,YU Jiwei,WU Jugang,LU Ruiqi,NI Xiaochun,WANG Shoulian,JIANG Bojian,.. Epithelial-Mesenchymal Transition Related Factors and CD133 Protein Expressions in Primary Lesion of Gastric Cancer and Its Relationship with Clinicopathologic Features and Prognosis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2013, 20(5): 492-498. doi: Copy

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1. Parkin DM， Bray F， Ferlay J， et al. Global cancer statistics， 2002[J]. CA Cancer J Clin， 2005， 55(2)：74-108.
2. Jemal A， Tiwari RC， Murray T， et al. Cancer statistics， 2004[J]. CA Cancer J Clin， 2004， 54(1)：8-29.
3. Thiery JP. Epithelial-mesenchymal transitions in tumour progression[J]. Nat Rev Cancer， 2002， 2(6)：442-454.
4. Thiery JP， Acloque H， Huang RY， et al. Epithelial-mesenchymaltransitions in development and disease[J]. Cell， 2009， 139(5)：871-890.
5. Takaishi S， Okumura T， Wang TC. Gastric cancer stem cells[J]. J Clin Oncol， 2008， 26(17)：2876-2882.
6. 陆瑞祺，俞继卫，姜波健，等. 胃癌CD133阳性细胞的纯化及其生物学特性的研究[J]. 中国普外基础与临床杂志， 2011， 18(12)：1265-1270.
7. Tsugane S， Sasazuki S. Diet and the risk of gastric cancer：reviewof epidemiological evidence[J]. Gastric Cancer， 2007， 10(2)：75-83.
8. Wheelock MJ， Johnson KR. Cadherins as modulators of cellular phenotype[J]. Annu Rev Cell Dev Biol， 2003， 19：207-235.
9. Chaffer CL， Weinberg RA. A perspective on cancer cell metastasis[J]. Science， 2011， 331(6024)：1559-1564.
10. Hay ED. The mesenchymal cell， its role in the embryo， and the remarkable signaling mechanisms that create it[J]. Dev Dyn，2005， 233(3)：706-720.
11. Thiery JP. Epithelial-mesenchymal transitions in development and pathologies[J]. Curr Opin Cell Biol， 2003， 15(6)：740-746.
12. Mani SA， Guo W， Liao MJ， et al. The epithelial-mesenchymal transition generates cells with properties of stem cells[J]. Cell， 2008， 133(4)：704-715.
13. Knutson KL， Lu H， Stone B， et al. Immunoediting of cancers may lead to epithelial to mesenchymal transition[J]. J Immunol，.
14. Wellner U， Schubert J， Burk UC， et al. The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs[J]. Nat Cell Biol， 2009， 11(12)：1487-1495.
15. Mehra N， Penning M， Maas J， et al. Progenitor marker CD133 mRNA is elevated in peripheral blood of cancer patients with bone metastases[J]. Clin Cancer Res， 2006， 12(16)：4859-4866.
16. Yu JW， Zhang P， Wu JG， et al. Expressions and clinical significances of CD133 protein and CD133 mRNA in primary lesion of gastric adenocacinoma[J]. J Exp Clin Cancer Res， 2010， 29：141.
17. Cano A， Pérez-Moreno MA， Rodrigo I， et al. The transcriptionfactor snail controls epithelial-mesenchymal transitions by repressingE-cadherin expression[J]. Nat Cell Biol， 2000， 2(2)：76-83.
18. ， 177(3)：1526-1533.

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Epithelial-Mesenchymal Transition Related Factors and CD133 Protein Expressions in Primary Lesion of Gastric Cancer and Its Relationship with Clinicopathologic Features and Prognosis

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