Expression And Prognostic Significance Of ERCC1, RRM1 And BRCA1 MRNA In Non-small-cell Lung Cancer

Background and purpose: Lung cancer is the leading cause of cancer death in the world. About 80% of lung cancers are no-small-cell lung cancer (NSCLC). Surgical resection is major therapeutic method of earlier stage lung cancer and most patients'prognosis is poor. Five year survival rate ofⅠa,Ⅰb,Ⅱa andⅡb stage patients is 70%,60%,55% and 40% respectively. With metastasis to ipsilateral mediastinal lymph node, patients'five year survival rate drops to 13%. Not all but some of patients get benefit from adjuvant chemotherapy, others are suffering to toxicity of chemotherapy without benefit from adjuvant chemotherapy. If we could find some biological marks that can help us pick up these patients. Than not only therapeutic effect would be increased, but also side effect would be avoided. Accordingly, we investigated the association between prognosis of lung cancer and the genes of ERCC1,RRM1 and BRCA1.Method: Thirty -one patients with stage IA to IIIB NSCLC randomly, who underwent complete surgical resection with curative intent between August 2003 and August 2004 at our hospital, were included in the study. Tissue specimens from these patients were collected and total RNA was extracted. Than cDNA was prepared by reverse transcription。We analyzed ERCC1, RRM1 and BRCA1 mRNA expression by real-time PCR. And ERCC1, RRM1 and BRCA1 expressions were normalized to humanβ-actin expression.Results: The expression levels of ERCC1, RRM1 and BRCA1 were significantly higher in lung cancer tissues than that in adjacent normal lung tissues. There were significant correlations between intratumoral expression of ERCC1, RRM1 and BRCA1. RRM1 expression levels were significantly higher in lung squamous cell carcinomas compared with adenocarcinomas but had no difference between different clinical stages. The expression of ERCC1 and BRCA1 had no difference between different pathological classifications and clinical TNM stages. The patients with high expression of RRM1 and BRCA1 had significant longer survival time than those with low expression of RRM1 and BRCA1. COX multivariate regression analysis showed that the expression of RRM1 was an independent prognostic factor for NSCLC.Conclusion: The expression levels of ERCC1, RRM1 and BRCA1 were significantly higher in lung cancer tissues than that in adjacent normal lung tissues. There were significant correlations between intratumoral expression of ERCC1, RRM1 and BRCA1. The patients with high expression of RRM1 and BRCA1 had significant longer survival time than those with low expression of RRM1 and BRCA1. Therefore, RRM1 and BRCA1 expression is potentially an important tool for use in cancer management and should be assessed for predicting differential chemosensitivity and tailoring chemotherapy in lung cancer.