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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。
BACKGROUND & OBJECTIVE: Epithelial-mesenchymal transition (EMT) is a key step in the process of tumor invasion and metastasis. The loss of epithelial cell polarity is the main sign of epithelial mesenchymal transition, which is characterized by the loss of epithelial markers such as Claudin. Zinc finger transcription factor Snail is an important transcription factor that regulates EMT. In recent years, it has been found that Snail can improve the invasiveness of many tumors. This study aimed to explore the expression and significance of Snail and Claudin-3 in non-small cell lung cancer (NSCLC) and their lymph node metastases by tissue microarray. Methods The expressions of Snail and Claudin-3 in 59 cases of normal lung tissue, 302 cases of NSCLC and 57 cases of lymph node metastasis were detected by immunohistochemistry MaxVision and EnVision. Results The expression of Snail in adjacent normal lung tissue, primary NSCLC and lymph node metastasis increased gradually (P <0.05). The expression of Claudin-3 in normal lung tissue, primary NSCLC and lymph node Metastasis in the expression gradually weakened, the difference was statistically significant (P <0.05). The expression of Snail and Claudin-3 in NSCLC primary tumor correlated with tumor histological type (P <0.05). Spearman rank correlation analysis showed that Snail and Claudin-3 expression was negatively correlated (r = -0.178, P = 0.002). Kaplan-Meier survival analysis showed that tumor size, histological type, histological grade, presence or absence of cancer metastasis, TNM staging, Snail expression and the differential expression of Snail and Claudin-3 affect the survival time of patients with NSCLC (P <0.05) . Cox regression analysis showed that tumor size, histological type, histological grade, presence or absence of cancer metastasis and TNM stage were independent risk factors for prognosis of patients with NSCLC (P <0.05). Conclusion Snail and Claudin-3 are important in the infiltration and metastasis of NSCLC, which is helpful to evaluate the prognosis of patients with NSCLC.