Abstract
PURPOSE: RRM1 is the large subunit of ribonucleotide reductase (RNR), which catalyzes the rate-limiting step in the production of deoxyribonucleotides (dNTPs) and is essential for DNA synthesis and repair. Through a meta-analysis of observational studies, we evaluated whether RRM1 expression levels are associated with the clinical outcome of gemcitabine-containing treatment regimens in patients with advanced non-small cell lung cancer (NSCLC). METHODS: A literature search was conducted using the PubMed, Embase, Web of Science, Wanfang and Chinese National Knowledge Infrastructure databases from inception to September 2014. A meta-analysis was conducted to pool eligible studies, and pooled analyses were performed using fixed effects models. RESULTS: A total of 12 studies encompassing 593 NSCLC patients met our search criteria and were, therefore, included. Pooled analyses revealed that patients with low/negative RRM1 expression levels exhibited significantly higher response rates (OR: 0.35, 95 % CI 0.24-0.51) and better survival rates (OR: 0.41, 95 % CI 0.23-0.75) than those with high/positive RRM1 expression levels. Subgroup analyses did not reveal any significant heterogeneity in outcome regarding the RRM1 assessment methods used or the ethnicities of patient populations studied. CONCLUSIONS: The meta-analysis reported here indicates that RRM1 expression is associated with the response rate and overall survival rate of advanced NSCLC patients treated with gemcitabine-based chemotherapy. Additional phase III randomized trials are required to confirm our current findings.