Abstract
Objective
To evaluate the predictive values of gene expressions of ribonucleotide reductase M1 (RRM1) and breast cancer susceptibility gene 1 (BRCA1) in peripheral blood from Chinese patients with non-small-cell lung cancer (NSCLC) treated with gemcitabine plus platinum.
Methods
Forty Chinese patients with advanced NSCLC were recruited and received gemcitabine 1 200 mg/m2 on Days 1 and 8 plus carboplatin AUC 5 on Day 1. RRM1 and BRCA1 expression levels in peripheral blood were detected by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Kaplan-Meier survival curve and log-rank test were performed to evaluate the correlation between gene expression and overall survival for these subjects.
Results
No correlation was observed between gene expression of RRM1 and that of BRCA1 (P>0.05), but there was a strong correlation between the expression of RRM1 and the response to chemotherapy (P=0.003). Subjects with low RRM1 expression levels in peripheral blood had longer survival time than those with high RRM1 expression levels (16.95 vs. 12.76 months, log-rank 3.989, P=0.046). However, no significant association between BRCA1 expression levels and survival time was found (16.80 vs. 13.77 months, log-rank 0.830, P=0.362).
Conclusions
Patients with low RRM1 expression levels in peripheral blood have a greater response to chemotherapy and longer survival time. Advanced NSCLC patients with low RRM1 expression levels may benefit from gemcitabine plus platinum therapy. RRM1 mRNA expression in peripheral blood could be used to predict the prognosis of NSCLC treated by gemcitabine and platinum.
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References
Ceppi, P., Volante, M., Novello, S., Rapa, I., Danenberg, K.D., Danenberg, P.V., Cambieri, A., Selvaggi, G., Saviozzi, S., Calogero, R., et al., 2006. ERCC1 and RRM1 gene expressions but not EGFR are predictive of shorter survival in advanced non-small-cell lung cancer treated with cisplatin and gemcitabine. Ann. Oncol., 17(12):1818–1825. [doi:10.1093/annonc/mdl300]
Davidson, J.D., Ma, L., Flagella, M., Geeganage, S., Gelbert, L.M., Slapak, C.A., 2004. An increase in the expression of ribonucleotide reductase large subunit 1 is associated with gemcitabine resistance in non-small cell lung cancer cell lines. Cancer Res., 64(11):3761–3766. [doi:10.1158/0008-5472.CAN-03-3363]
Dong, S., Guo, A.L., Chen, Z.H., Wang, Z., Zhang, X.C., Huang, Y., Xie, Z., Yan, H.H., Cheng, H., Wu, Y.L., 2010. RRM1 single nucleotide polymorphism −37C→A correlates with progression-free survival in NSCLC patients after gemcitabine-based chemotherapy. J. Hematol. Oncol., 3(1):10. [doi:10.1186/1756-8722-3-10]
Gautam, A., Li, Z.R., Bepler, G., 2003. RRM1-induced metastasis suppression through PTEN-regulated pathways. Oncogene, 22(14):2135–2142. [doi:10.1038/sj.onc.1206232]
Goan, Y.G., Zhou, B., Hu, E., Mi, S., Yen, Y., 1999. Overexpression of ribonucleotide reductase as a mechanism of resistance to 2,2-difluorodeoxycytidine in the human KB cancer cell line. Cancer Res., 59(17):4204–4207.
Isla, D., Sarries, C., Rosell, R., Alonso, G., Domine, M., Taron, M., Lopez-Vivanco, G., Camps, C., Botia, M., Nunez, L., et al., 2004. Single nucleotide polymorphisms and outcome in docetaxel-cisplatin-treated advanced non-small-cell lung cancer. Ann. Oncol., 15(8):1194–1203. [doi:10.1093/annonc/mdh319]
Jemal, A., Siegel, R., Ward, E., Murray, T., Xu, J., Thun, M.J., 2007. Cancer statistics, 2007. CA Cancer J. Clin., 57(1): 43–66. [doi:10.3322/canjclin.57.1.43]
Quinn, J.E., Kennedy, R.D., Mullan, P.B., Gilmore, P.M., Carty, M., Johnston, P.G., Harkin, D.P., 2003. BRCA1 functions as a differential modulator of chemotherapy-induced apoptosis. Cancer Res., 63(19):6221–6228.
Quinn, J.E., James, C.R., Stewart, G.E., Mulligan, J.M., White, P., Chang, G.K., Mullan, P.B., Johnston, P.G., Wilson, R.H., Harkin, D.P., 2007. BRCA1 mRNA expression levels predict for overall survival in ovarian cancer after chemotherapy. Clin. Cancer Res., 13(24):7413–7420. [doi:10.1158/1078-0432.CCR-07-1083]
Rosell, R., Scagliotti, G., Danenberg, K.D., Lord, R.V., Bepler, G., Novello, S., Cooc, J., Crino, L., Sanchez, J.J., Taron, M., et al., 2003. Transcripts in pretreatment biopsies from a three-arm randomized trial in metastatic non-small-cell lung cancer. Oncogene, 22(23):3548–3553. [doi:10.1038/sj.onc.1206419]
Rosell, R., Danenberg, K.D., Alberola, V., Bepler, G., Sanchez, J.J., Camps, C., Provencio, M., Isla, D., Taron, M., Diz, P., et al., 2004a. Ribonucleotide reductase messenger RNA expression and survival in gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients. Clin. Cancer Res., 10(4):1318–1325. [doi:10.1158/1078-0432.CCR-03-0156]
Rosell, R., Felip, E., Taron, M., Majo, J., Mendez, P., Sanchez-Ronco, M., Queralt, C., Sanchez, J.J., Maestre, J., 2004b. Gene expression as a predictive marker of outcome in stage IIB-IIIA-IIIB non-small cell lung cancer after induction gemcitabine-based chemotherapy followed by resectional surgery. Clin. Cancer Res., 10(12 Pt 2):4215s–4219s. [doi:10.1158/1078-0432.CCR-040006]
Rosell, R., Skrzypski, M., Jassem, E., Taron, M., Bartolucci, R., Sanchez, J.J., Mendez, P., Chaib, I., Perez-Roca, L., Szymanowska, A., et al., 2007. BRCA1: a novel prognostic factor in resected non-small-cell lung cancer. PLoS One, 2(11):e1129. [doi:10.1371/journal.pone.0001129]
Taron, M., Rosell, R., Felip, E., Mendez, P., Souglakos, J., Ronco, M.S., Queralt, C., Majo, J., Sanchez, J.M., Sanchez, J.J., et al., 2004. BRCA1 mRNA expression levels as an indicator of chemoresistance in lung cancer. Hum. Mol. Genet., 13(20):2443–2449. [doi:10.1093/hmg/ddh260]
Wang, L.R., Wu, X.H., Huang, M.Z., Cai, J., Xu, N., Liu, J., 2007a. The efficacy and relationship between peak concentration and toxicity profile of fixed-dose-rate gemcitabine plus carboplatin in patients with advanced non-small-cell lung cancer. Cancer Chemother. Pharmacol., 60(2):211–218. [doi:10.1007/s00280-006-0363-x]
Wang, L.R., Huang, M.Z., Zhang, G.B., Xu, N., Wu, X.H., 2007b. Phase II study of gemcitabine and carboplatin in patients with advanced non-small-cell lung cancer. Cancer Chemother. Pharmacol., 60(4):601–607. [doi:10.1007/s00280-007-0504-x]
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Project supported by the Science and Technology Planning Project of Zhejiang Province (No. 2009C33165) and the Medical Science Research Fund Scheme of Zhejiang Province (No. 2008A060), China
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Wang, Lr., Zhang, Gb., Chen, J. et al. RRM1 gene expression in peripheral blood is predictive of shorter survival in Chinese patients with advanced non-small-cell lung cancer treated by gemcitabine and platinum. J. Zhejiang Univ. Sci. B 12, 174–179 (2011). https://doi.org/10.1631/jzus.B1000197
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DOI: https://doi.org/10.1631/jzus.B1000197
Key words
- Gemcitabine
- Ribonucleotide reductase M1 (RRM1)
- Breast cancer susceptibility gene 1 (BRCA1)
- Non-small-cell lung cancer (NSCLC)
- Gene expression