RRM1 and ERCC1 expression in peripheral blood versus tumor tissue in gemcitabine/carboplatin-treated advanced non-small cell lung cancer
- 631 Downloads
To comparatively evaluate the prognostic or predictive value of ribonucleotide reductase M1 (RRM1) and excision repair cross-complementation 1 (ERCC1) gene expression in peripheral blood versus tumor tissue from patients with advanced non-small cell lung cancer (NSCLC) treated by gemcitabine/platinum chemotherapy.
A total of 49 patients with advanced NSCLC receiving gemcitabine plus carboplatin chemotherapy were studied. RRM1 and ERCC1 mRNA levels in the peripheral blood and tumor tissue were determined by real-time fluorescent quantitative PCR. The relationships between gene expression and clinical and pathological factors, response to chemotherapy as well as prognosis, were evaluated.
RRM1 expression in peripheral blood and tumor tissue, but not ERCC1 expression, was found to be positively correlated (r = 0.332, 0.258; P = 0.020, 0.073; respectively). RRM1 and ERCC1 expression levels were nearly synchronous in both peripheral blood (r = 0.351; P = 0.013) and tumor tissue (r = 0.634; P < 0.001). Neither was correlated with clinical and pathological factors. Patients with low RRM1 expression in peripheral blood or low RRM1 or ERCC1 expression in tumor tissue experienced better response to chemotherapy (50.0 vs. 16.0%, 50.0 vs. 16.0%, and 54.2 vs. 12.0%; P = 0.012, 0.012, and 0.003; respectively), longer median survival (18.5 vs. 13.0 months, 18.5 vs. 12.0 months, and 19.8 vs. 12.5 months; P = 0.043, 0.014 and 0.007; respectively), and longer progression-free survival (6.0 vs. 4.0 months, 7.8 vs. 3.9 months, and 5.8 vs. 3.8 months; P = 0.044, 0.016, and 0.008; respectively). Cox multivariate regression analysis showed that ERCC1 expression in tumor tissue was independent indicator for overall survival.
Advanced NSCLC patients with low RRM1 mRNA expression both in peripheral blood and in tumor tissue could benefit from gemcitabine/carboplatin chemotherapy. ERCC1 mRNA expression in tumor tissue may be a predictive and prognostic indicator in advanced NSCLC patients receiving gemcitabine/carboplatin chemotherapy.
KeywordsRRM1 ERCC1 Gemcitabine Non-small cell lung cancer Real-time fluorescent quantitative PCR
This work is supported by the Science and Technology Planning Project of Zhejiang Province (No. 2009C33165), the Medical Science Research Fund Scheme of Zhejiang Province (No. 2008A060), and the Chinese Medicine General Research Program of Zhejiang Province (2009CA061).
Conflicts of interest
None of the authors have any conflicts of interest.
- 5.Lee JJ, Maeng CH, Baek SK et al (2010) The immunohistochemical overexpression of ribonucleotide reductase regulatory subunit M1 (RRM1) protein is a predictor of shorter survival to gemcitabine-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Lung Cancer 70:205–210PubMedCrossRefGoogle Scholar
- 12.Chen J, Li MW, Zhang GB et al (2010) Detection of RRM1, ERCC1 and BRCA1 gene expression in non-small cell lung cancer tissues and peripheral blood by SYBR real-time fluorescent quantitative PCR. J Zhejiang Univ Med Sci 39:628–633Google Scholar
- 13.Gong WY, Zhang XM, Wu JF et al (2011) RRM1 expression and clinical outcome of gemcitabine-containing chemotherapy for advanced non-small-cell lung cancer: A meta-analysis. Lung Cancer [Epub ahead of print]Google Scholar
- 15.Roth JA, Carlson JJ (2011) Prognostic role of ERCC1 in advanced non-small-cell lung cancer: a systematic review and meta-analysis. Clin Lung Cancer [Epub ahead of print]Google Scholar
- 18.Lin L, Liu XQ, Wang WX et al (2008) Detection of gemcitabine-resistant genes expression in six lung cancer cell lines using real-time fluorogenetic quantitative PCR. Tumor 28:228–231Google Scholar
- 19.Li LL, Liu XQ (2010) Correlation of expression of ERCC1/RRM1 with cisplatin combined with gemcitabine chemotherapy sensitivity and prognosis in non-small cell lung cancer. Bull Acad Mil Med Sci 34:265–268, 296Google Scholar
- 21.Dong S, Wu YL, Guo AL et al (2007) Detection of expression of RRM1 mRNA by real-time fluorescent quantitative PCR in non-small cell lung cancer tissues and peripheral blood. Tumor 27:577–581Google Scholar
- 22.Wang LE, Yin M, Dong Q et al. (2011) DNA repair capacity in peripheral lymphocytes predicts survival of patients with non-small cell lung cancer treated with first-line platinum-based chemotherapy. J Clin Oncol [Epub ahead of print]Google Scholar