应用组织芯片研究肺癌多药耐药相关基因的表达及临床意义  

The expression and significance of the multidrug resistance-related proteins P-gp, MRP, LRP and GST-π in lung cancer using tissue microarray

作　　者：吴胜勇[1] 吴佩宁[1] 张绍明[1] 段德溥[1] 

机构地区：[1]中国人民解放军第455医院胸外科,上海200052

出　　处：《中国癌症杂志》2008年第8期611-619,共9页China Oncology

摘　　要：背景与目的:肺癌的耐药性是影响肺癌化疗效果的重要因素,但是到目前为止,尚无有效的解决办法。本研究旨在通过检测耐药基因蛋白P-糖蛋白(P-gp)、多药耐药相关蛋白(MRP)、肺耐药相关蛋白(LRP),谷胱甘肽硫转酶(GST-π)在肺癌组织中的表达,探讨耐药基因间的相互关系及在临床中对肺癌诊断、治疗及患者预后的意义。方法:采用组织芯片技术制作226例肺癌组织及23例正常肺组织芯片,并用S-P法免疫组化检测组织芯片中耐药基因蛋白P-gp、MRP、LRP和GST-π的表达。结果:在226例肺癌组织中P-gp、MRP、LRP和GST-π表达的阳性率分别为46.0%、42.0%、54.4%、62.4%,正常肺组织中分别为17.4%、13.0%、17.4%、21.7%,两组间差异有显著性(P<0.001);中高分化非小细胞癌与低分化非小细胞癌、非小细胞癌(NSCLC)与小细胞癌(SCLC)相比,差异有显著性(P<0.05),其中中高分化非小细胞癌的阳性表达分别为59.7%、58.1%、73.6%、79.1%,低分化非小细胞癌分别为33.3%、22.8%、33.3%、47.4%,非小细胞癌分别为51.6%、47.3%、61.3%、69.4%,小细胞癌分别为20.0%、17.5%、22.5%、30.0%;P-gp、MRP、GST-π的阳性率由高到低依次为腺癌、鳞癌、小细胞癌,相对应临床化疗敏感性由低到高;术前化疗病例(84.1%、61.9%、69.8%、93.7%)高于未化疗者(31.3%、34.4%、48.5%、50.3%),两组间差异有显著性(P<0.05);术后复发转移的P-gp和GST-π阳性率(55.7%、71.1%)高于无复发转移者(31.4%、47.1%),MRP、LRP虽然也高于后者,但差异无显著性(分别χ2=3.08及1.37,P>0.05)。结论:肺癌耐药由多基因及多途径参与发生,联合检测肺癌组织中耐药相关基因的表达有助于判断化疗疗效及预后。应用组织芯片大规模高效检测肺癌组织样本是可行的。Background and purpose： Resistance to anticarcinogen is one of the key factors that affect the treatment efficiency in lung cancer. The purpose of this study was to investigate the clinical significance of the multidurg resistance-related proteins P-gp, multidrug resistance-related proteins（MRP）,lung resistance associated protien（LRP） and GST-πby detecting their expression in lung cancer and to investigate the mechanism of resistance to anticarcinogen. Methods： S-P immunohistochemistry was used to examine the expression level of proteins P-gp, MRP, LRP and GST- πin 226 samples of lung cancer and 23 samples of normal lung tissues. Results： The positive rates of P-gp, MRP, LRP and GST-π in lung cancers were 46.0%, 42.0%, 54.4%, 62.4% respectively. Significant difference existed between tumorous tissue and normal lung tissue （17.4%, 13.0%, 17.4%, 21.7%）. The positive rates of P-gp, MRP, LRP and GST-π in poorly differentiated-type of NSCLC were 33.3%, 22.8%, 33.3%, 47.4%, compared with differentiated-type of NSCLC （59.7%, 58.1%, 73.6%, 79.1%） （P〈0.05）, The positive rates of P-gp, MRP, LRP and GST-π in NSCLC vs. SCLC were （51.6%, 47.3%, 61.3%, 69.4%） vs.（20.0%, 17.5%, 22.5%, 30.0%） （P〈0.05）. In addition, the expression rates of P-gp, MRP and GST-π were highest in adenocarcinoma, followed by squamous carcinoma and small-cell carcinoma, which were consistent with the cells＇ sensitivity to chemotherapy. Besides, the expression intensity of P-gp,MRP, LRP and GST-π in samples treated by chemotherapy （84.1%, 61.9%, 69.8%,93.7%） was significantly stronger than the samples without chemotherapy （P〈0.05）;and there was significant difference in the expression rates of P-pg and GST-π rather than MRP and LRP between the cases with and without recurrence and metastasis after surgery （55.7%, 71.1%）. Conclusion： The mechanism of lung cancer resistance to chemotherapy may involve many genes and signal pathways. Combined evaluation of the expression rates of these gene

关 键 词：组织芯片 免疫组织化学 肺肿瘤 多药耐药 多药耐药相关蛋白 P-糖蛋白 肺耐药相关蛋白 谷胱甘肽转酶 

分 类 号：R734.2[医药卫生—肿瘤]