三种肿瘤耐药基因在非小细胞肺癌中的表达及临床意义

The expression of LRP,MRP and MDR1 in non-small-cell lung cancer and their clinical significance

目的探讨肺耐药蛋白(Lung resistance protein,LRP),多药耐药蛋白(Multidrug resistance-associated protein,MRP)和多药耐药基因(Multidrug resistance,MDR1)的mRNA在非小细胞肺癌(Non-small cell cancer,NSCLC)中共表达及临床意义。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、MDR1 mRNA阳性率分别为71.2%、81.8%和37.9%;MRP与、MDR1、MRP与LRP、LRPYU MDR1及MRP、LRPYU MDR1共表达者分别为16.7%(11/66)、53.0%(35/66)、19.7%(13/66)及12.1%(8/66)。LRP与MRP阳性相关(r=0.47,p=0.001),LRP、MRP与MDR1无相关性(r=0.98,p=0.077;r=0.25,p=0.053).3种耐药基因表达在NSCLC各期、各分化组中差异无显著性(P≥0.05)。肺腺癌换了有效组LRP、MRP mRNA(0.53±0.08;0.41±0.01)及鳞癌化疗有效组LRP mRNA表达(0.42±0.03)明显低于换了无效组(1.14±0.3,0.82±0.04,0.97±0.01,P<0.05);LRP与MRP、LRP、MRP与MDR1共表达者,中位生存期明显缩短(P<0.05)。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、MRP、MDR1共同作用有关。

Objective To determine the expression of lung resistance protein （LRP）, multidrng resistance - associated protein （MRP）and multidrng resistance 1（MDR1mma ）,and discuss its clinical significance in non- small- cell lung cancer（NSCLC）. Methods RT- RCR was used to determine the expression of mma of the above mentioned genes. Results The frequency of expression of LRP, MRP and MDR 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 correlation was found neither between LRP and MDR1, nor between MRP and MDR. The expression of LRP, MRP and MDR1 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 chemotherapy 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 redusced. Conclusion The intrinsic multidrng resistance of NSCLC involves the combined effects of LRP, MRP and MDR.