Expression And Clinical Significance Of Drug-Resistant Related Genes In Non-Small Cell Lung Cancer

Objective:To study the expression levels of MRP1,LRP,BCRP and ERCC1 mRNA in patients with non-small cell lung cancer(NSCLC) as well as their clinicopathological significance.Methods:RT-PCR semi-quantitative method were used to detecte the expression levels of MRP1,LRP,BCRP and ERCC1 mRNA in tumor tissues samples and corresponding adjacent normal lung tissues of 60 patients with NSCLC.Correlation of MRP1,LRP,BCRP and ERCC1mRNA expression levels with sex,age,smoking history,histopathologic type,cells differentiated degree and stage TNM in NSCLC patiets were analysized.Relationships between patients prognosis and MRP1,LRP,BCRP or ERCC1 mRNA expression levels were evaluated. T-Test,One-Way ANOVA,Spearman correlation,Kaplan-Meier survivalcurve and Cox multivariate regression analysis were used for statistical analysis.Results:(1)The expression levels of MRP1,LRP and ERCC1 mRNA were significantly higher in NSCLC tissues than that in adjacent normal lung tissues(P=0.02,=0.000 and=0.025,respectively).The expression levels of BCRPmRNA was significantly higher in adjacent normal lung tissues than that in NSCLC tissues(P=0.042).There were significant correlations between BCRP mRNA expression level in tumor tissue and adjacent normal lung tissue(r_s=0.339,P=0.008). There were significant correlations between intratumoral expression of MRP1 and LRP mRNA(r_s=0.543,P=0.000)as well as BCRP and ERCC1 mRNA(r_s=0.317,P=0.014).(2)MRP1 mRNA expression level was significantly higher in patients with tumor diameter＞3cm,as compared with≤3cm(P=0.013).There were no significantly relationships among sex,age,smoking,differentiation,lymphaden metastasis,pathological classification and TNM stages. LRP mRNA expression level was significantly higher in lung adenocarcinomas than in squamous carcinoma(P=0.02),and higher in cancer tissue of well-differentiated than in that of poorly differentiated(P=0.033).There was no difference between LRP mRNA expression level and other clinicopathologic parameters.The expression levels of BCRP mRNA and ERCC1mRNA were not related to any clinicopathologic parameters.(3)The patients with low expression of MRP1 mRNA had significantly longer median survival time than those with high expression of MRP1 mRNA(P=0.023).Cox multivariate regression analysis showed that expression of MRP1 mRNA was an independent prognostic factor for NSCLC(RR=4.784, P=0.026)Conclusion:(1)These multidrug-resistance associated factors may play roles in the intrinsic multidrug resistance of NSCLC in some extent,in which BCRP may be of an unimportant roles in primary MDR phenomena.(2)There are some relationship among the expression of MRP1,LRP,BCRP and ERCCl in NSCLC intratumoral,which suggest that these factors may related with the developement of MDR.(3) Some of these multi drug-resistance associated factors correlated with the size of tumor,the histopathologic type,cell differentiated degrees and patients prognosis.(4)It is significance to detect the expression levels of these drug-resistance associated factors for the prediction of the intrinsic multidrug resistance and the guidance of individualized chemical therapy in NSCLC patients.