Expression of epithelial-mesenchymal transition and cancer stem cell markers in colorectal adenocarcinoma: Clinicopathological significance
Expression of epithelial-mesenchymal transition and cancer stem cell markers in colorectal adenocarcinoma: Clinicopathological significance
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DOI：
10.3892/or.2017.5790
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发表时间：
2017-09-01
期刊：
影响因子：
4.2
通讯作者：
Moon, Woo Sung
中科院分区：
文献类型：
--
作者：
Choi, Ji Eun;Bae, Jun Sang;Moon, Woo Sung
上皮-间质转化（EMT）与癌症进展、转移扩散和治疗耐药性有关，并发生在侵袭性前沿。肿瘤干细胞（cancer stem cells，CSCs）具有干细胞特征，可能参与肿瘤的发生、局部复发和转移。本研究旨在探讨EMT和CSC相关蛋白在原发性结直肠癌（CRC）不同肿瘤部位的表达状况、相互关系及其沿着临床病理意义。我们使用组织芯片对286例原发性结直肠癌患者的两个不同肿瘤区域（代表性肿瘤中心和最深浸润前沿）的4种EMT相关蛋白（即E-cadherin、beta-catenin、snail和vimentin）和两种CSC相关蛋白（即CD 44和CD 133）进行免疫组织化学染色。所有EMT相关蛋白的表达改变在侵袭性前沿比在肿瘤中心更频繁地观察到。E-cadherin、beta-catenin和vimentin的表达改变与侵袭性肿瘤特征显著相关。特别是，在浸润前沿E-钙粘蛋白表达的缺失与较短的无病生存期（DFS，P=0.002）和总生存期（OS，P=0.007）显著相关。浸润前沿波形蛋白的过表达与OS差显著相关（P=0.028）。CD 44在肿瘤中心和浸润前沿的表达缺失与不利的临床病理特征显著相关。在浸润前沿，而不是在肿瘤中心，E-cadherin，β-catenin，vimentin，snail和CD 133的蛋白表达模式的改变与侵袭性临床病理因素和较短的DFS（P=0.003）和OS（P=0.005）显著相关。目前的数据表明，表达改变的EMT和CSC相关蛋白组合的癌细胞可能代表侵袭性肿瘤行为的潜在生物标志物，并且可能成为未来CRC分子靶向治疗的可能候选者。
Epithelial-mesenchymal transition (EMT) is known to be associated with cancer progression, metastatic spread, and therapeutic resistance and to occur at the invasive front. Cancer stem cells (CSCs) display stemness features and might be implicated in tumor initiation, local recurrence and metastasis. The present study was conducted to examine the expression status and relationships between EMT-and CSC-related proteins in the different tumor areas of primary colorectal cancer (CRC), along with their clinicopathological significance. We performed immunohistochemical staining for 4 EMT-related proteins, namely E-cadherin, beta-catenin, snail and vimentin, and two CSC-related proteins, namely CD44 and CD133, in two different tumor areas (the representative tumor center and the deepest invasive front) in 286 cases of primary CRC using tissue microarrays. Altered expression of all EMT-related proteins was more frequently observed in the invasive front than in the tumor center. Altered expression of E-cadherin, beta-catenin and vimentin significantly associated with aggressive tumor characteristics. In particular, loss of E-cadherin expression in the invasive front significantly associated with shorter disease-free survival (DFS, P=0.002) and overall survival (OS, P=0.007). Overexpression of vimentin in the invasive front significantly correlated with poor OS (P=0.028). Loss of CD44 expression both in the tumor center and in the invasive front significantly associated with unfavorable clinicopathological characteristics. In the invasive front, but not in the tumor center, combination of the altered protein expression patterns of E-cadherin, beta-catenin, vimentin, snail and CD133 significantly associated with aggressive clinicopathological factors and shorter DFS (P=0.003) and OS (P=0.005). The present data suggest that cancer cells expressing a combination of altered EMT-and CSC-related proteins may represent a potential biomarker for aggressive tumor behavior and may be a possible future candidate for molecular targeted treatments for CRC.