Background and objective: 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.
Methods: 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.
Results: 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).
Conclusions: 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.
背景与目的: 上皮-间质转化（epithelial mesenchymal transition, EMT）是肿瘤浸润和转移的关键步骤，上皮细胞极性丧失是其主要标志，表现为Claudin等上皮标记丢失。锌指转录因子Snail是调控EMT的重要转录因子，近年来对肿瘤侵袭转移机制研究发现Snail能提高多种肿瘤的侵袭能力。本研究旨在利用组织芯片技术探讨转录因子Snail和紧密连接蛋白（Claudin-3）在非小细胞肺癌（non-small cell lung cancer, NSCLC）及其淋巴结转移灶中的表达和意义。
方法: 分别采用免疫组织化学MaxVision法和EnVision法检测59例癌旁正常肺组织、302例NSCLC原发灶以及57例淋巴结转移灶中Snail和Claudin-3的表达。
结果: Snail在癌旁正常肺组织、NSCLC原发灶以及淋巴结转移灶中的表达逐渐增强，差异具有统计学意义（P < 0.05）；Claudin-3在癌旁正常肺组织、NSCLC原发灶以及淋巴结转移灶中的表达逐渐减弱，差异具有统计学意义（P < 0.05）。在NSCLC原发灶中，Snail和Claudin-3的表达与肿瘤组织学类型有关（P < 0.05）。Spearman等级相关分析显示Snail与Claudin-3的表达呈负相关（r=-0.178, P=0.002)。Kaplan-Meier生存分析显示肿瘤大小、组织学类型、病理分级、有无癌转移、TNM分期、Snail的表达以及Snail与Claudin-3的差异性表达影响NSCLC患者的术后生存时间（P < 0.05）。Cox回归分析提示肿瘤大小、组织学类型、病理分级、有无癌转移和TNM分期是影响NSCLC患者预后的独立危险因素（P < 0.05）。
结论: Snail和Claudin-3在NSCLC的浸润、转移中具有重要意义，有助于对NSCLC患者预后的评价。