osteopontin在非小细胞肺癌中的异常表达及其临床意义  

Over-expression of osteopontin in non-small cell lung cancers:its clinical significance

作　　者：胡智[1] 肖汀[1] 林冬梅[2] 郭素萍[3] 张自强[4] 邸雪冰[3] 程书钧[3] 高燕宁[3] 

机构地区：[1]中国医学科学院中国协和医科大学肿瘤医院肿瘤研究所病因及癌变研究室,北京100021 [2]中国医学科学院中国协和医科大学肿瘤医院病理科,北京100021 [3]中国医学科学院 中国协和医科大学 肿瘤医院肿瘤研究所病因及癌变研究室,北京100021 [4]中国医学科学院中国协和医科大学肿瘤医院中心实验室,北京100021

出　　处：《中华肿瘤杂志》2007年第8期591-595,共5页Chinese Journal of Oncology

基　　金：国家973规划资助项目(2004CB518705);北京市科技计划资助项目(D0905001040731);高等学校博士学科点专项科研基金(20030023005)

摘　　要：目的探讨细胞外基质蛋白分子osteopontin(OPN)在非小细胞肺癌(NSCLC)中的表达状况及特点,以及其在肺癌发生演进中的作用及其临床意义。方法35例新鲜NSCLC肿瘤及其对照肺组织,采用逆转录PCR(RT-PCR)技术,分析OPN基因在RNA水平的表达改变。大样本石蜡包埋组织(662个有效样品的组织微阵列)以免疫组织化学染色,检测OPN蛋白在NSCLC中的表达状况,并分析其与肿瘤的组织学及临床特征的关系。结果RT-PCR分析显示,OPN在80.0%的NSCLC肿瘤组织中转录上调。免疫组化染色分析显示,OPN蛋白在肿瘤组织中的表达(59.6%)显著高于正常肺组织(25.2%,P<0.001),且OPN在鳞癌中的表达高于腺癌。通过对鳞癌的深入分析则表明,OPN蛋白表达水平在有淋巴结转移和无淋巴结转移的原发癌间有统计学意义(68.6%和49.7%,P= 0.001),而在同一组患者的原发癌和淋巴结转移癌之间的表达水平则趋于一致(68.6%和75.5%,P=0.171)。结论OPN在NSCLC(尤其是鳞癌)中表达水平明显升高,其过表达与肺鳞癌淋巴结转移密切相关,增加了肿瘤转移的风险(OR=2.212);OPN有促进肺癌恶性演进的作用。Objective Data obtained from a differentially expressed cDNA library constructed previously in this laboratory demonstrated that the extracellular matrix molecule osteopontin （OPN） is one of most considerably over-expressed genes in non-small cell lung cancers （ NSCLCs ）. The purpose of the present study was to explore the expression status of OPN in a large scale NSCLC tissue samples, and estimate its significance in progression of the malignant disease. Methods RT-PCR was performed with the tumor and adjacent normal tissues from 35 patients with NSCLC, at transcriptional levels of OPN. To determine the expression of OPN protein in the tumor tissues, immunohistochemical （ IHC ） staining was subsequently carried out on paraffin-embedded sections in tissue microarrays containing 662 samples derived from NSCLC cases. The correlation between the expression level of OPN and clinical characteristics was analyzed statistically. Results Comparing with the paired normal lung tissue, high level RNA of OPN was detected in 80.0% （ 28/35 ） of the NSCLC tumor tissues by RT-PCR, which confirmed the information obtained previously by our differentially expressed cDNA library. The results of IHC analysis showed that positively stained OPN protein was observed in 59. 6% （331/555） of the tumor tissues, which was remarkably higher than that （25.2% , 27/107） detected in the normal control tissues （P 〈 0. 001 ）. Among the NSCLCs investigated, over-expressed OPN was more frequently found in squamous cell carcinomas （SCCs） than in adenocarcinomas. A further analysis on SCCs demonstrated that the rate of over-expressed OPN was significantly different between the primary tumors with and without lymphatic metastases （68.6% vs. 49.7%, P = 0. 001 ）, but similar in the primary tumors and their corresponding metastases in lymph nodes （68.6% vs. 75.5%, P = 0. 171 ）. Conclusion Expression of OPN protein is distinctly increased in NSCLCs, particularly in SCCs. OPN over-expression is considerably correlat

关 键 词：细胞外基质蛋白分子 OSTEOPONTIN 非小细胞肺癌 

分 类 号：R734.2[医药卫生—肿瘤]