Li Juan, Tu Yuan, Jiang Lili, Xu Huan, Zhang Shangfu
Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, China.
Zhongguo Fei Ai Za Zhi. 2012 Oct;15(10):583-90. doi: 10.3779/j.issn.1009-3419.2012.10.04.
Epithelial-mesenchymal transition (EMT) is considered to be one of the major molecular mechanisms inducing tumor invasion and metastasis. The loss of epithelial cell polarity is a hallmark of the EMT process. Epithelial markers such as Claudin are lost in EMT. Snail is a major transcription factor governing EMT. Recent studies about the mechanism of tumor invasion and metastasis has proven that Snail could enhance the ability of many tumors' invasiveness. The aim of this study is to investigate the expression of Snail and Claudin-3 in non-small cell lung cancer (NSCLC) and its metastatic lymph node with tissue microarray technique, and to explore clinical significance of these two molecules expression in NSCLC.
Snail and Claudin-3 proteins were detected in cases of 59 adjacent normal lung tissues, 302 cases of primary NSCLC and 57 cases of lymph node metastatic tissues by MaxVision and EnVision method of immunohistochemical staining respectively.
The expression of Snail in adjacent normal lung tissues, NSCLC primary foci and metastatic lymph node appeared upward tendency (P<0.05), and the expression of Claudin-3 in adjacent normal lung tissues, NSCLC primary foci and metastatic lymph node appeared weakened (P<0.05). Further more, expression 1evel of Snail and Claudin-3 proteins in NSCLC were related to the histological type (P<0.05). The Spearman correlation analysis showed that the expression of Snail and Claudin-3 was negatively correlated (r=-0.178, P=0.002). Kaplan-Meier survival analysis indicated that factors such as the tumor size, histological type, grading, metastasis, TNM staging, and difference expression between two proteins were associated with the postoperative survival rate of NSCLC patients (P<0.05). Multivariate analysis using Cox regression model identified that the tumor size, histological type, grading, metastasis and TNM staging were independent prognostic factors of NSCLC patients (P<0.05).
Snail and Claudin-3 may play important roles in invasion and metastasis in NSCLC, So might be employed to evaluate the prognosis of NSCLC patients.
上皮-间质转化（EMT）被认为是诱导肿瘤侵袭和转移的主要分子机制之一。上皮细胞极性的丧失是EMT过程的一个标志。上皮标志物如Claudin在EMT过程中丢失。Snail是调控EMT的主要转录因子。近期关于肿瘤侵袭和转移机制的研究证实，Snail可增强多种肿瘤的侵袭能力。本研究旨在采用组织芯片技术探讨Snail和Claudin-3在非小细胞肺癌（NSCLC）及其转移淋巴结中的表达情况，并探究这两种分子表达在NSCLC中的临床意义。
分别采用免疫组织化学染色的MaxVision法和EnVision法检测59例肺组织正常对照、302例原发性NSCLC及57例淋巴结转移组织中Snail和Claudin-3蛋白的表达。
Snail在肺组织正常对照、NSCLC原发灶及转移淋巴结中的表达呈上升趋势（P<0.05），Claudin-3在肺组织正常对照、NSCLC原发灶及转移淋巴结中的表达呈减弱趋势（P<0.05）。此外，NSCLC中Snail和Claudin-3蛋白的表达水平与组织学类型有关（P<0.05）。Spearman相关性分析显示，Snail与Claudin-3的表达呈负相关（r=-0.178，P=0.002）。Kaplan-Meier生存分析表明，肿瘤大小、组织学类型、分级、转移、TNM分期以及两种蛋白的差异表达等因素与NSCLC患者术后生存率有关（P<0.05）。采用Cox回归模型进行多因素分析，结果显示肿瘤大小、组织学类型、分级、转移及TNM分期是NSCLC患者的独立预后因素（P<0.05）。
Snail和Claudin-3可能在NSCLC侵袭和转移中发挥重要作用，可用于评估NSCLC患者的预后。
