The predictive role of E2-EPF ubiquitin carrier protein in esophageal squamous cell carcinoma
The predictive role of E2-EPF ubiquitin carrier protein in esophageal squamous cell carcinoma
复制标题
DOI：
10.1007/s00109-008-0430-3
复制
发表时间：
2009-03-01
影响因子：
4.7
通讯作者：
Chen, Wen-Cheng
中科院分区：
文献类型：
--
作者：
Chen, Miao-Fen;Lee, Kuan-Der;Chen, Wen-Cheng
泛素蛋白酶体途径与癌症发生有关。然而，E2-EPF泛素载体蛋白（UCP）在食管癌中的作用仍然相对缺乏研究。在这项研究中，我们检测了来自60名食管癌患者的循环肿瘤细胞的mRNA水平，通过由一组潜在标记物（包括UCP）组成的膜阵列，与40名正常人群进行比较。通过对84例活检食管鳞状细胞癌的回顾性系列的免疫组化染色，评估UCP的预测能力与临床结局的关系。此外，我们研究了体外生物学变化，包括肿瘤生长，转移能力，以及对放射和顺铂的敏感性，实验操作后UCP在食管癌细胞中的表达。25基因膜阵列分析结果显示，UCP是唯一与食管癌患者肿瘤负荷程度显著相关的因素。我们的免疫化学结果进一步表明，UCP阳性与新辅助治疗反应差和生存率差有关。在细胞培养中，抑制UCP显著降低肿瘤生长和转移能力。VHL/HIF-1 α-TGF-β 1通路诱导的上皮-间质转化（EMT）可能是UCP阳性食管癌侵袭性生长的机制之一。我们的研究结果表明，UCP与食管癌的不良预后显着相关，并可能成为一个新的分子靶点，为食管鳞癌的治疗干预。
The ubiquitin proteasome pathway has been implicated in carcinogenesis. However, the role of E2-EPF ubiquitin carrier protein (UCP) in esophageal cancer remains relatively unstudied. In the study, we examined the mRNA level of circulating tumor cells from 60 esophageal cancer patients by membrane arrays consisting of a panel of potential markers including UCP, compared to 40 normal populations. The predictive capacity of UCP was also assessed by immunohistochemical staining of a retrospective series of 84 biopsied esophageal squamous cell carcinomas in relation to clinical outcome. In addition, we studied in vitro biological changes including tumor growth, metastatic capacity, and the sensitivity to irradiation and cisplatin, after experimental manipulation of UCP expression in esophageal cancer cells. By the data of 25-gene membrane array analysis, UCP was the only factor significantly associated with the extent of tumor burden in esophageal cancer patients. Our immunochemistry findings further indicate that UCP positivity was linked to poor response to neoadjuvant therapy and worse survival. In cell culture, inhibited UCP significantly decrease tumor growth and the capacity for metastasis. The epithelial-mesenchymal transition (EMT) induced by VHL/HIF-1 alpha-TGF-beta 1 pathway might be the underlying mechanism responsible to the more aggressive tumor growth in UCP-positive esophageal cancer. Our results suggest that UCP was significantly associated with poor prognosis of esophageal cancer and may be a new molecular target for therapeutic intervention for esophageal squamous cell carcinoma.