Combination of epithelial-mesenchymal transition and cancer stem cell-like phenotypes has independent prognostic value in gastric cancer
Combination of epithelial-mesenchymal transition and cancer stem cell-like phenotypes has independent prognostic value in gastric cancer
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DOI：
10.1016/j.humpath.2011.07.003
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发表时间：
2012-04-01
期刊：
影响因子：
3.3
通讯作者：
Lee, Hye Seung
中科院分区：
文献类型：
--
作者：
Ryu, Han Suk;Park, Do Joong;Lee, Hye Seung
上皮-间充质转化相关蛋白已被认为在各种癌症中相互作用，并与癌症的侵袭行为有关。为了证明胃癌上皮-间质转化和干细胞样表型的临床意义，我们对276例连续原发性胃癌和54例匹配的淋巴结转移患者进行了5种上皮-间质转化相关蛋白（包括Snail-1、ZEB-1、E-cadherin、vimentin和β -catenin）和胃癌干细胞标志物CD44的免疫组织化学检测。E-cadherin表达缺失和vimentin异常表达与侵袭性临床病理特征显著相关。胃癌组织中上皮-间质转化相关蛋白的表达密切相关。已知胃癌干细胞制造因子CD44与Snail-1、ZEB-1、E-cadherin蛋白表达显著相关（P < 0.05）。对纳入本研究的6种蛋白进行单因素生存分析，以寻找预测患者预后的最佳组合。Kaplan-Meier法显示，Snail-1、vimentin、E-cadherin和CD44蛋白的表达P值最低（P < 0.001）。在高危组中，这种蛋白组合与晚期pT分期、淋巴结转移、血管侵犯和未分化的组织学类型显著相关（P < 0.001），并预测与pTNM分期和组织学分化无关的无病生存（P = 0.029）。然而，胃癌细胞在原发部位的获得性间充质表型在淋巴结转移中恢复为上皮表型。上皮-间质转化和干细胞样表型的结合是侵袭性生物学行为的重要预测因子，在预测原发性胃癌的预后方面具有独立的预后价值。(C) 2012爱思唯尔公司版权所有。
Epithelial-mesenchymal transition related proteins have been suggested to interact with each other in various cancers and be associated with the aggressive behavior of cancer. To demonstrate the clinical significance of epithelial-mesenchymal transition and stem cell like phenotypes in gastric cancer, we performed immunohistochemistry for 5 epithelial-mesenchymal transition related proteins, including Snail-1, ZEB-1, E-cadherin, vimentin, and beta-catenin, and the gastric cancer stem cell marker CD44 in 276 consecutive primary gastric cancers and 54 matched lymph node metastases. Loss of E-cadherin expression and aberrant expression of vimentin were significantly associated with aggressive clinicopathologic features. The expression of epithelial-mesenchymal transition related proteins was closely related to each other in gastric cancer. The known gastric cancer stem cell maker, CD44, was significantly associated with the protein expression of Snail-1, ZEB-1, and E-cadherin (P < .05). Univariate survival analysis was performed for the 6 proteins included in this study to find the best combination for predicting patient outcome. Protein expression of Snail-1, vimentin, E-cadherin, and CD44 resulted in the lowest P value using the Kaplan-Meier method (P < .001). This combination of proteins was significantly associated with advanced pT stage, lymph node metastasis, vascular invasion, and undifferentiated histologic type in a high-risk group (P < .001) and predicted disease-free survival independent of pTNM stage and histologic differentiation (P = .029). However, the acquired mesenchymal phenotype of gastric cancer cells at the primary site was restored to an epithelial phenotype in lymph node metastases. A combination of epithelial-mesenchymal transition and stem cell like phenotypes is an important predictor of aggressive biologic behavior and has an independent prognostic value in predicting outcomes of primary gastric cancer. (C) 2012 Elsevier Inc. All rights reserved.