• 上海交通大學醫(yī)學院附屬第三人民醫(yī)院普外一科(上海 201900);

目的  研究上皮間質轉化(EMT)相關因子Snail、E-cadherin、N-cadherin與胃癌患者臨床病理特征、預后及胃癌腫瘤起始細胞表面標志物CD133表達的關系。
方法  利用Western blot方法檢測50例胃癌及癌旁正常胃黏膜組織中EMT相關因子及CD133蛋白的定位及定量表達,分析EMT相關因子及CD133蛋白表達與胃癌患者的臨床病理學指標的關系,Spearman等級相關分析EMT相關因子和CD133表達的關系,Kaplan-Meier方法分析EMT相關因子及CD133表達與胃癌患者生存的關系。
結果 ?、傥赴┙M織中Snail、N-cadherin及CD133蛋白表達相對灰度值明顯高于其在癌旁正常胃黏膜組織中的表達(Snail:0.599±0.114比0.259±0.108,P=0.020;N-cadherin:0.754±0.154比0.329±0.134,P=0.001;CD133:0.635±0.119比0.485±0.116,P=0.029),E-cadherin蛋白表達相對灰度值明顯低于其在癌旁正常胃黏膜組織中的表達(0.378±0.123比0.752±0.156,P=0.003)。②Snail蛋白、N-cadherin蛋白表達平均相對灰度值在有血管浸潤、淋巴管浸潤、N3淋巴結轉移及腫瘤直徑≥5 cm和Ⅲ+Ⅳ期胃癌患者中的表達明顯高于無血管浸潤、淋巴管浸潤、N0~N2淋巴結轉移及腫瘤直徑<5 cm和Ⅰ+Ⅱ期的胃癌患者(P<0.05),而E-cadherin蛋白表達平均相對灰度值在有血管浸潤、淋巴管浸潤、N3淋巴結轉移及Ⅲ+Ⅳ期胃癌患者中的表達顯著低于無血管浸潤、淋巴管浸潤、N0~N2淋巴結轉移及Ⅰ+Ⅱ期的胃癌患者(P<0.05),CD133蛋白表達平均相對灰度值在有淋巴管浸潤、N3淋巴結轉移、腫瘤直徑≥5 cm和Ⅲ+Ⅳ期胃癌患者中的表達顯著高于無淋巴管浸潤、N0~N2淋巴結轉移、腫瘤直徑<5cm和Ⅰ+Ⅱ期的胃癌患者(P<0.05)。③Snail、N-cadherin蛋白表達與CD133蛋白表達分別均呈正相關(rs=0.278,P=0.048;rs=0.406,P=0.003),而E-cadherin蛋白表達與CD133蛋白表達呈負相關(rs=-0.504,P=0.000)。④Snail、N-cadherin及CD133蛋白低表達組的生存時間明顯長于其高表達者 (P<0.05),聯(lián)合EMT相關因子和CD133蛋白表達能夠最有效預測患者生存。
結論  EMT與胃癌腫瘤起始細胞特性之間存在明顯相關,并且兩者與胃癌的高侵襲的臨床病理特征相關,聯(lián)合EMT相關因子Snail、E-cadherin、N-cadherin與CD133能夠最有效預測胃癌患者的預后。

引用本文: 蔡成,俞繼衛(wèi),吳巨鋼,陸瑞祺,倪曉春,王守練,姜波健. 胃癌原發(fā)灶中上皮間質轉化相關因子和CD133的表達及其與臨床病理特征和預后的關系△. 中國普外基礎與臨床雜志, 2013, 20(5): 492-498. doi: 復制

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6. 陸瑞祺, 俞繼衛(wèi), 姜波健, 等. 胃癌CD133陽性細胞的純化及其生物學特性的研究[J]. 中國普外基礎與臨床雜志, 2011, 18(12):1265-1270.
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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.
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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.
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18. , 177(3):1526-1533.
  1. 1. Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002[J]. CA Cancer J Clin, 2005, 55(2):74-108.
  2. 2. Jemal A, Tiwari RC, Murray T, et al. Cancer statistics, 2004[J]. CA Cancer J Clin, 2004, 54(1):8-29.
  3. 3. Thiery JP. Epithelial-mesenchymal transitions in tumour progression[J]. Nat Rev Cancer, 2002, 2(6):442-454.
  4. 4. Thiery JP, Acloque H, Huang RY, et al. Epithelial-mesenchymaltransitions in development and disease[J]. Cell, 2009, 139(5):871-890.
  5. 5. Takaishi S, Okumura T, Wang TC. Gastric cancer stem cells[J]. J Clin Oncol, 2008, 26(17):2876-2882.
  6. 6. 陸瑞祺, 俞繼衛(wèi), 姜波健, 等. 胃癌CD133陽性細胞的純化及其生物學特性的研究[J]. 中國普外基礎與臨床雜志, 2011, 18(12):1265-1270.
  7. 7. Tsugane S, Sasazuki S. Diet and the risk of gastric cancer:reviewof epidemiological evidence[J]. Gastric Cancer, 2007, 10(2):75-83.
  8. 8. Wheelock MJ, Johnson KR. Cadherins as modulators of cellular phenotype[J]. Annu Rev Cell Dev Biol, 2003, 19:207-235.
  9. 9. Chaffer CL, Weinberg RA. A perspective on cancer cell metastasis[J]. Science, 2011, 331(6024):1559-1564.
  10. 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. 11. Thiery JP. Epithelial-mesenchymal transitions in development and pathologies[J]. Curr Opin Cell Biol, 2003, 15(6):740-746.
  12. 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. 13. Knutson KL, Lu H, Stone B, et al. Immunoediting of cancers may lead to epithelial to mesenchymal transition[J]. J Immunol,.
  14. 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. 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. 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. 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. 18. , 177(3):1526-1533.
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