非小细胞肺癌中整合素和ECM蛋白表达与转移及预后的相关性研究

Expression of Integrins and Extracellular Matrix Proteins in Non-small Cell Lung Cancer: Correlation with Tumor Metastasis and Prognosis

背景与目的肿瘤的浸润和转移严重威胁着人类生命,正确认识和评估肿瘤的生物学行为有重要的临床意义。整合素和细胞外基质(ECM)的异常表达在肿瘤浸润转移过程中发挥着重要作用。本研究的目的是探讨整合素α5、β1(integrinα5、β1)与细胞外基质(ECM)在人非小细胞肺癌(NSCLC)中的表达及其与淋巴结转移及患者预后之间的关系,评估它们在肿瘤转移过程中的作用。方法采用免疫组化方法测定119例NSCLC组织中整合素α5、β1及Ⅳ型胶原、纤连蛋白(fibronectin,FN)、细胞黏合素的表达,探讨其与临床病理特征特别是与淋巴结转移的关系,并分析其与患者预后的相关性。结果Ⅳ型胶原表达与淋巴结转移呈负相关(P<0.01),与患者预后呈正相关(P<0.01),而整合素α5和β1表达与淋巴结转移呈正相关(P<0.01),且整合素α5表达与患者预后呈负相关(P<0.01)。整合素α5表达与整合素β1表达呈正相关而与Ⅳ型胶原表达呈负相关。Ⅳ型胶原在分期较早和分化较好时表达率较高,整合素α5和β1则相反。结论整合素α5和β1的高表达与ECM蛋白的低表达与NSCLC的淋巴结转移及患者不良预后相关,整合素α5与Ⅳ型胶原可能可以作为评估患者预后的重要指标。

Background and objective As invasion and metastasis of cancer seriously threaten human＇s life, it is of more important clinical significance to understand and evaluate the biologic behavior of cancer correctly. Abnormal expression of integrin and ECM proteins play an important role in invasion and metastasis of cancer. The objective of this study is to analyze the expression of the integrin α5, β1 and ECM proteins in patients with NSCLC and its correlation with lymph node （LN） metastasis as well as prognosis, and to evaluate its roles in the metastasis of tumor. Methods The expression of integrin α5, β1 and collagen type Ⅳ, fibronectin, tenascin was determined by immunohistochemistry. The relationship was analysized that between integrin α5, β1 and ECM proteins expression and elinieo-pathologie parameters especially LN metastasis and prognosis. Results The expression of collagen type IV was negatively correlated with LN metastasis, and positively to prognosis of patients; The expression of integrin α5, β1 was positively correlated with LN metastasis, and integrin α 5 was negatively to prognosis of patients. The expression of integrin α5 was positively correlated with the expression of integrin β1, and negatively with the expression of collagen type Ⅳ. The expression of collagen type Ⅳ in stage Ⅰ disease P-TNM stage was remarkably higher than that in stage Ⅲ disease and poordifferentiated disease （P〈0.001）, but integrin α5, β1 was significantly higher than that in stage Ⅲ disease and poor- differentiated disease. Conclusion Increased expression of integrin α5, β1 and decreased expression of ECM significantly correlated with LN metastasis of NSCLC. Integrin α5 and collagen type Ⅳ are prognosic factors in patients with NSCLC.