Xu Ming-Ming, Mao Guo-Xin, Liu Jian, Li Jian-Chao, Huang Hua, Liu Yi-Fei, Liu Jun-Hua
Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China E-mail :
Asian Pac J Cancer Prev. 2014;15(9):4013-8. doi: 10.7314/apjcp.2014.15.9.4013.
Because of its importance in tumor invasion and metastasis, the epithelial-mesenchymal transition (EMT) has become a research focus in the field of cancer. Recently, evidence has been presented that FoxO4 might be involved in EMT. Our study aimed to detect the expression of FoxO4, E-cadherin and vimentin in non-small cell lung cancers (NSCLCs). We also investigated clinical features and their correlations with the markers. In our study, FoxO4, E-cadherin and vimentin were assessed by immunohistochemistry in a tissue microarray (TMA) containing 150 cases of NSCLC. In addition, the expression level of FoxO4 protein was determined by Western blotting. The percentages of FoxO4, E-cadherin and vimentin positive expression in NSCLCs were 42.7%, 38.7% and 55.3%, respectively. Immunoreactivity of FoxO4 was low in NSCLC when compared with paired normal lung tissues. There were significant correlations between FoxO4 and TNM stage (P<0.001), histological differentiation (P=0.004) and lymph node metastasis (P<0.001), but no significant links with age (P=0.323), gender (P=0.410), tumor size (P=0.084), smoking status (P=0.721) and histological type (P=0.281). Our study showed that low expression of FoxO4 correlated with decreased expression of E-cadherin and elevated expression of vimentin. Cox regression analysis indicated FoxO4 to be an independent prognostic factor in NSCLC (P=0.046). These data suggested that FoxO4 might inhibit the process of EMT in NSCLC, and might therefore be a target for therapy.
由于上皮-间质转化（EMT）在肿瘤侵袭和转移中具有重要作用，它已成为癌症领域的研究热点。最近，有证据表明FoxO4可能参与EMT过程。我们的研究旨在检测非小细胞肺癌（NSCLC）中FoxO4、E-钙黏蛋白和波形蛋白的表达情况。我们还研究了临床特征及其与这些标志物的相关性。在我们的研究中，通过免疫组织化学方法在包含150例NSCLC病例的组织微阵列（TMA）中评估了FoxO4、E-钙黏蛋白和波形蛋白。此外，通过蛋白质印迹法测定了FoxO4蛋白的表达水平。NSCLC中FoxO4、E-钙黏蛋白和波形蛋白阳性表达的百分比分别为42.7%、38.7%和55.3%。与配对的正常肺组织相比，NSCLC中FoxO4的免疫反应性较低。FoxO4与TNM分期（P<0.001）、组织学分化（P=0.004）和淋巴结转移（P<0.001）之间存在显著相关性，但与年龄（P=0.323）、性别（P=0.410）、肿瘤大小（P=0.084）、吸烟状态（P=0.721）和组织学类型（P=0.281）无明显关联。我们的研究表明，FoxO4低表达与E-钙黏蛋白表达降低和波形蛋白表达升高相关。Cox回归分析表明FoxO4是NSCLC的独立预后因素（P=0.046）。这些数据表明，FoxO4可能抑制NSCLC中的EMT过程，因此可能成为治疗靶点。
