Platinum-based drugs (cisplatin, etc.) are used as a first-line therapy for NSCLC patients. However, such treatment is not effective for all patients. Biomarkers that could predict efficiency of the platinum-based treatment should be identified. Aim: To evaluate whether the response to treatment of NSCLC patients is based on ERCC1 and RRM1 gene expression in bronchial washing fluid.
70 patients with a first-time diagnosed NSCLC receiving Cisplatin+Etoposid were involved in the study. RNA was extracted from bronchial washing fluid using “RNeasy Plus Mini Kit” (QIAGEN, Germany). The analysis of ERCC1 and RRM1 expression was done by qRT-PCR method. A χ2 test was used to analyze gene expression in relation to clinicopathological parameters. The survival rates were calculated by the Kaplan-Meier method. The prognostic significance was assessed by the Cox proportional hazards regression model.
Statistically significant differences were found between ERCC1 expression and tumour differentiation grade, RRM1 expression and disease stage and lymph node status. ERCC1 expression was associated with NSCLC patient progression-free survival (PFS) rate depending on gender, disease stage, response to treatment. Patients from high ERCC1 expression group had 7.6 months longer survival than patients from low expression group. RRM1 expression was associated with NSCLC patients PFS rates depending on gender, age, tumour histology and differentiation grade. Patients from low RRM1 expression group had 7.9 months longer survival than those from high expression group. Multivariate analysis of factors influencing PFS rate showed that disease stage (p = 0.01), tumor differentiation grade (p = 0.009), response to treatment (p = 0.02) and RRM1 expression (p = 0.001) were independent prognostic factors of NSCLC patients PFS.
ERCC1 and RRM1 genes may influence platinum-based chemotherapy treatment of NSCLC patients. In order to improve the effectiveness of treatment it is appropriate to identify RRM1 expression changes in the bronchial washing fluid. Therefore, NSCLC patients with high RRM1 expression should be actively followed-up because of quicker disease progression.
Clinical trial identification
Lithuanian Bioethics Committee No. 158200-09-381-104
Legal entity responsible for the study
National Cancer Institute
All authors have declared no conflicts of interest.