LRP、MRP、MDR_1基因在非小细胞肺癌中的表达及其临床意义

Expression of LRP, MRP and MDR_1 in non small-cell lung cancer and its clinical significance

目的 探讨肺耐药蛋白 (lungresistanceprotein ,LRP)、多药耐药蛋白 (multidrugresistance associatedprotein ,MRP)和多药耐药基因 (multidrugresistance ,MDR1)mRNA在非小细胞肺癌 (non smallcellcancer,NSCLC)中的共表达及临床意义。方法 RT PCR检测NSCLC冰冻组织中上述耐药基因的mRNA水平。结果 LRP、MRP、MDR1mRNA阳性率分别为 74.2 % (4 9/ 6 6 )、80 .3% (5 3/ 6 6 )和 37.9%(2 5 / 6 6 ) ;MRP与MDR1、MRP与LRP、LRP与MDR1及MRP、LRP与MDR1共表达者分别为 16 .7% (11/6 6 )、5 3.0 % (35 / 6 6 )、19.7% (13/ 6 6 )及 12 .1% (8/ 6 6 )。LRP与MRP阳性相关 (r =0 .47,P =0 .0 0 1) ,LRP、MRP与MDR1无相关性 (r=0 .98,P =0 .0 77;r =0 .2 5 ,P =0 .0 5 3)。 3种耐药基因表达在NSCLC各期、各分化组中差异无显著性 (P≥ 0 .0 5 )。肺腺癌化疗有效组LRP、MRPmRNA(0 .5 3± 0 .0 8,0 .41±0 .0 1)及鳞癌化疗有效组LRPmRNA表达 (0 .42± 0 .0 3)明显低于化疗无效组 (1.14± 0 .3,0 .82± 0 .0 4,0 .97± 0 .0 1,P <0 .0 5 ) ;LRP与MRP ,LRP、MRP与MDR1共表达者 ,中位生存期明显缩短 (P <0 .0 5 )。多变量Cox回归分析 ,仅LRP +MRP、LRP +MRP +MDR1共表达有预后意义。结论 非小细胞肺癌原发耐药与LRP?

Objective To detect expression of lung resistance protein(LRP), multidrug resistance associated protein(MRP) and multidrug resistance 1(MDR 1) mRNA, and its clinical significance in non small cell lung cancer (NSCLC).Methods RT PCR was used to investigate mRNA expression of the above mentioned genes. Results The frequency of expression of LRP, MRP and MDR 1 was 74.2%, 80.3% and 37.9%, respectively. A significant positive correlation was observed between LRP and MRP( r =0.47, P =0.001), but this association was found neither between LRP and MDR 1, nor between MRP and MDR 1. The expression of LRP, MRP and MDR 1 did not vary with the grade of cell differentiation and TNM staging. In adenocarcinomas which responded to chemotherapy, there was lowered expression of both LRP and MRP than those which did not respond. In chemo responsive aquamous cell carcinomas, however, this was true of LRP expression only. The median survival time of NSCLC patients with co expressed 2 and 3 drug resistance related genes was significantly reduced. Conclusion The intrinsic multidrug resistance of NSCLC involves the combined effects of LRP, MRP and MDR 1.