OPN在肺鳞癌组织中高表达及其临床意义

Expression of OPN protein in lung squamous cell carcinoma tissue and its clinical significance

背景与目的：骨桥蛋白（osteopontin，OPN）是一种分泌型磷酸化糖蛋白，在多种肿瘤组织中异常高表达，与肿瘤的发生、发展及预后有密切关系。当肿瘤细胞侵袭细胞外基质时，OPN可通过NF-κB依赖的信号转导通路促进肿瘤细胞高表达基质金属蛋白酶（matrix metal protease，MMPs），引起细胞基底膜和细胞外基质降解，从而导致肿瘤发生浸润和转移。该研究通过检测肺鳞状上皮细胞癌（lung squamous cell carcinoma， SCC）患者肿瘤组织中OPN的蛋白水平，研究其与各临床指标的关系及其意义。方法：采用免疫组织化学染色法检测265例石蜡包埋的肺SCC组织和24例正常肺组织中OPN蛋白表达水平。结果：OPN在肺SCC组织表达阳性率为64.5%，显著高于正常肺组织（阳性率为29.2%，P〈0.001）。OPN在肺SCC晚期（Ⅲ＋Ⅳ期）表达阳性率为78.4%，显著高于早期（Ⅰ＋Ⅱ期）组织（阳性率为54.5%，P〈0.001）。在T3-4分期的肺SCC组织中OPN表达阳性率为76.9%，显著高于T1-2分期（59.4%，P=0.007）。OPN的表达与肺SCC的淋巴结转移情况显著相关，在有淋巴结转移的癌组织中表达阳性率为73.4%，高于无淋巴结转移的癌组织（阳性率为51.4%，P〈0.001）。结论：OPN参与肺SCC的发生、发展和淋巴结转移，提示其在肺SCC的诊断、判断预后及治疗方面具有重要参考价值。

Background and purpose：Osteopontin （OPN） is a secreted glyco-phosphoprotein, which is overex-pressed by numerous human cancers, invovled in tumor occurrence, development and prognosis. OPN up-regulates matrix metal proteases （MMPs） expression in a NF-κB-dependent fashion during extracellular matrix （ECM） invasion causing degradation of cell basement membrane and ECM leading to tumor invasion and metastasis. The aim of this study was to examine the protein level of OPN in a large number of tissue samples from patients with lung squamous cell carcinoma （SCC）, and evaluate its potential clinical value.Methods：The OPN protein levels in 265 tumor tissue samples and corresponding 24 normal lung tissue samples were examined by immunohistochemical （IHC） analysis.Results：IHC results showed that the positive rate of OPN was 64.5% in the SCC tissues, which was significantly higher than that in normal alveoli tissues （29.2%,P〈0.001）. The positive rate of OPN expression in late stage （Ⅲ＋Ⅳ） tissues was 78.4%, significantly higher than that in early stage （Ⅰ＋Ⅱ） tissue（positive rate 54.5%,P〈0.001）. The positive rate of OPN expression in T3-4 stage （Ⅲ＋Ⅳ） tissue was 76.9%, significantly higher than that in T1-2 stage tissue （positive rate 59.4%,P=0.007）. The expression of OPN was signifcantly correlated with the status of lymph node metastasis （LNM）. The positive rate in the tumor tissue with LNM was 73.4%, significantly higher than that without （positive rate 51.4%,P〈0.001）.Conclusion：The level of OPN protein was overexpressed in lung cancer tissues, involved in SCC carcinogenesis and LNM. It is indicated that OPN has an impor-tant reference value in diagnosis, prognosis and therapy of SCC.