Expression Of ERCC1 MRNA In Peripheral Blood And Sensitivity Of Cisplatin-based Chemotherapy In Advanced Non-Small Cell Lung Cancer

Objective: Cisplatin-based Combination chemotherapy has been the primary therapy in advanced non small-cell lung cancer (NSCLC).A plenty of studies indicated that an important mechanism of the sensitivity to platinum involves is DNA repair capacity (DRC). The nucleotide excision repair pathway (NER) is the main pathway to repair platinum-DNA adducts caused by chemotherapy. Excision repair cross-complementing 1 (ERCC1) gene, which codes for the crucial rate-limiting end nuclease in NER pa- thway, is involved in the resistance to platinum. Some researchers sugge- sted that there was a close relation between the expression of ERCC1 mRNA and the therapeutic effect of platinum.This study tried to develop a method of detecting the expression levels of ERCC1 mRNA in peripheral blood by fluorescent real-time RT-PCR, investigate the correlation of the sensitivity of platinum-based chemothe- rapy in advanced non small-cell lung cancer, provide the basis for predict- ting clinical outcome from the expression of ERCC1 mRNA.Methods: 30 patients were diagnosed as NSCLC by pathological examination of percutaneous needle mass aspiration or bronchofiberscopy biopsy. The relative quality analysis of ERCC1 mRNA in peripheral blood specimen was performed by the extractive technique of RNA and SYBR Green I fluorescent real-time quantitative RT-PCR assay before chemo- therapy. The patients recieved 4 to 6 cycles of cisplatin-based chemotherapy (GC or DC regimen). The response rate (RR) was evaluated as the chemotherapy finished using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Results: Expression of ERCC1 mRNA was detectable in all patients. The total response rate of cisplatin-based chemotherapy (PR/PR+SD+PD) was 30% and the total disease control rate (PR+SD/PR+SD+PD)was 86%;Expression of ERCC1 mRNA in the chemosensitive patients(median level 1.79,the scope from 1.023 to 2.987) is obviously lower than those in the chemoresistant patient(smedian level 2.779,the scope from 1.000 to 5.099), (Z=2.376,P=0.017, Mann-Whitney Test)Expression of ERCC1 mRNA was gradually higher in PR,SD,PD patient groups(median level 1.79,2.883,3.545, respectively),there was statistical significant deviation among three groups(H=6.319,P=0.042,Kruskal-Wallis Test).There was significant difference in response rate of chemotherapy between the patients with low ERCC1 mRNA expression (RR)and high ERCC1 mRNA expression(RR: 53.3% vs 6.6%),(P=0.014,Fisher,s Exact Test)。However,There was no significant difference in disease control rate between the patients with low ERCC1 mRNA expression and high ERCC1 mRNA expression,( P=1.000 Fisher,s Exact Test)。Conclusion: There was negative correlation between ERCC1 mRNA expression in peripheral blood of response rate in advanced NSCLC patients. The expression of ERCC1mRNA in non-small cell lung cancer was succe- ssfully detected by using SYBR Green I fluorescent real-time quantitative RT-PCR assay. This detecting method has relatively higher sensitivity and specificity and can be used for clinical analysis.