SHP2在吸烟肺癌患者肿瘤组织中的表达及意义

Expression and Clinical Significance of SHP2 in the Tumor Tissues of Smokers with Lung Cancer

背景与目的蛋白质的磷酸化和去磷酸化是肺癌发生的重要机制,而吸烟是导致肺癌发生发展的重要危险因素,本研究旨在探讨蛋白酪氨酸磷酸酶SHP2在非小细胞肺癌(non-small cell lung cancer,NSCLC)和小细胞肺癌(small cell lung cancer,SCLC)肿瘤组织中的表达及其临床意义,并初步探讨不同的吸烟指数与SHP2表达水平的关系及可能机制。方法采用免疫组织化学技术(Invision法)和荧光原位杂交技术(FISH法)检测53例肺癌组织中SHP2的表达和SHP2mRNA的扩增情况。结果 SHP2在15例正常支气管上皮内弱阳性率为80%(亦为总阳性率);在48例NSCLC中弱阳性率为35.4%,中度阳性率为43.8%,强阳性率为6.2%(总阳性率为85.4%);在5例SCLC中弱阳性率为0%,中度阳性率为80%,强阳性率为20%(总阳性率为100%)。SHP2在27例非吸烟NSCLC患者肿瘤组织中的弱阳性率为40.7%,中度阳性率为37.4%,强阳性率为3.7%(总阳性率为81.5%);SHP2在吸烟指数≥400的21例NSCLC患者肿瘤组织中弱阳性率为23.8%,中度阳性率为71.4%,强阳性率为4.7%(总阳性率为100%)。等级计数资料秩和检验结果表明,肺癌组织中SHP2表达的阳性率显著高于正常支气管上皮(P<0.05),SCLC中SHP2的阳性率高于NSCLC(P<0.05),吸烟指数≥400的NSCLC癌组织中SHP2阳性率高于非吸烟患者(P<0.05)。结论吸烟NSCLC患者肿瘤组织中SHP2的高表达可能与吸烟相关;SHP2可能在肺癌发生发展中起一定的作用;SHP2可能为肺癌治疗的药物研发提供新思路。

Background and objective It has been proved that protein phosphorylation and dephosphorylation were important mechanisms in lung cancer development,and tobacco smoking is an important risk factor of lung cancer.The aim of this study is to investigate the expression and clinical significance of protein tyrosine phosphatase SHP2 in non-small cell lung cancer（NSCLC） and small cell lung cancer（SCLC）;the relationship between tobacco smoking and the expression of SHP2 is also studied.Methods Immunohistochemistry（Invision） and fluorescence in situ hybridization（FISH） were used to detect the expression of SHP2 and the augment of SHP2 mRNA in the 53 lung cancer specimens.Results The weak positive rate of SHP2 was 80%（which was also the total positive rate） in normal bronchial epithelium.The weak,moderate and strong positive rates were 35.4%,43.8% and 6.2%（total positive rate was 85.4%） in 48 NSCLC patients,0%,80% and 20%（total positve rate was 100%） in 5 SCLC patients,40.7%,37.4% and 3.7%（total positive rate was 81.5%） in the tumor tissues of 27 NSCLC patients who didn＇t smoke and 23.8%,71.4% and 4.7%（total positive rate was 100%） in the tumor tissues of 21 NSCLC patients whose smoking indexes were≥400.Significant differences of SHP2 expression were observed between tumor tissues and normal bronchial epithelium,NSCLC and SCLC,and between different smoking indexes（P〈0.05）.Conclusion The enhancement of SHP2 expression in the tumor tissues of NSCLC patients who smoke may be correlated with tobacco smoking;SHP2 may play certain role in the development of lung cancer;SHP2 prospectively provides new ideas for the drug research and development of lung cancer treatment.