Journal of Experimental & Clinical Cancer Research | |
Combined analysis of mRNA expression of ERCC1, BAG-1, BRCA1, RRM1 and TUBB3 to predict prognosis in patients with non-small cell lung cancer who received adjuvant chemotherapy | |
Man-Hong Li3  Guang-Yao Ma2  Lei Dai1  Lei Xian1  Ming-Wu Chen1  Xue-Feng Leng1  | |
[1] Department of Cardiothoracic Surgery, The First Afflicted Hospital of Guangxi Medical University, 22# Shuangyong Road, Qingxiu Region 530021 Nanning, China;Department of Cardiothoracic Surgery, The First Afflicted Hospital of Luohe Medical college, 462000 Luohe, China;Department of Cardiothoracic Surgery, Central Hospital of Loudi, 417000 Loudi, China | |
关键词: TUBB3; RRM1; BRCA1; BAG-1; ERCC1; Non-small cell lung cancer; | |
Others : 826715 DOI : 10.1186/1756-9966-31-25 |
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received in 2012-01-17, accepted in 2012-03-23, 发布年份 2012 | |
【 摘 要 】
Background
The aim of this study was to investigate prognostic value of excision repair cross-complementing 1 (ERCC1), BCL2-associated athanogene (BAG-1), the breast and ovarian cancer susceptibility gene 1 (BRCA1), ribonucleotide reductase subunit M1 (RRM1) and class III β-tubulin (TUBB3) in patients with non-small cell lung cancer (NSCLC) who received platinum- based adjuvant chemotherapy.
Methods
Messenger RNA expressions of these genes were examined in 85 tumor tissues and 34 adjacent tissue samples using semi-quantitative RT-PCR. The expressions of these five genes were analyzed in relation to chemotherapy and progression-free survival (PFS) and overall survival (OS). Seventy-four patients were enrolled into chemotherapy.
Results
Patients with ERCC1 or BAG-1 negative expression had a significantly longer PFS (P = 0.001 and P = 0.001) and OS (P = 0.001 and P = 0.001) than those with positive expression. Patients with negative ERCC1 and BAG-1 expression benefited more from platinum regimen (P = 0.001 and P = 0.002). Patients with BRCA1 negative expression might have a longer OS (P = 0.052), but not PFS (P = 0.088) than those with BRCA1 positive expression. A significant relationship was observed between the mRNA expression of ERCC1 and BAG-1 (P = 0.042). In multivariate analysis, ERCC1 and BAG-1 were significantly favorable factors for PFS (P = 0.018 and P = 0.017) and OS (P = 0.027 and P = 0.022).
Conclusions
ERCC1 and BAG-1 are determinants of survival after surgical treatment of NSCLC, and its mRNA expression in tumor tissues could be used to predict the prognosis of NSCLC treated by platinum.
【 授权许可】
2012 Leng et al; licensee BioMed Central Ltd.
【 预 览 】
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【 参考文献 】
- [1]Chen W, Zhang S, Zou X: Evaluation on the incidence, mortality and tendency of lung cancer in China. Thoracic Cancer 2010, 1:35-40.
- [2]Olaussen KA, Dunant A, Fouret P, Brambilla E, Andre F, Haddad V, Taranchon E, Filipits M, Pirker R, Popper HH, et al.: DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med 2006, 355:983-991.
- [3]Takayama S, Sato T, Krajewski S, Kochel K, Irie S, Milian JA, Reed JC: Cloning and functional analysis of BAG-1: A novel Bcl-2-binding protein with anti-cell death activity. Cell 1995, 80:279-284.
- [4]Krajewska M, Turner BC, Shabaik A, Krajewski S, Reed JC: Expression of BAG-1 protein correlates with aggressive behavior of prostate cancers. Prostate 2006, 66:801-810.
- [5]Liu H, Liang Y, Li Y, Wang J, Wu H, Wang Y, Tang SC, Chen J, Zhou Q: Gene silencing of BAG-1 modulates apoptotic genes and sensitizes lung cancer cell lines to cisplatin-induced apoptosis. Cancer Biol Ther 2010, 9:832-840.
- [6]Kennedy RD, Quinn JE, Johnston PG, Harkin DP: BRCA1: mechanisms of inactivation and implications for management of patients. Lancet 2002, 360:1007-1014.
- [7]Bepler G, Gautam A, McIntyre LM, Beck AF, Chervinsky DS, Kim YC, Pitterle DM, Hyland A: Prognostic significance of molecular genetic aberrations on chromosome segment 11p15.5 in non-small-cell lung cancer. J Clin Oncol 2002, 20:1353-1360.
- [8]Bepler G, Kusmartseva I, Sharma S, Gautam A, Cantor A, Sharma A, Simon G: RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer. J Clin Oncol 2006, 24:4731-4737.
- [9]Dumontet C, Isaac S, Souquet PJ, Bejui-Thivolet F, Pacheco Y, Peloux N, Frankfurter A, Luduena R, Perol M: Expression of class III beta tubulin in non-small cell lung cancer is correlated with resistance to taxane chemotherapy. Bull Cancer 2005, 92:E25-E30.
- [10]Azuma K, Sasada T, Kawahara A, Takamori S, Hattori S, Ikeda J, Itoh K, Yamada A, Kage M, Kuwano M, Aizawa H: Expression of ERCC1 and class III [beta]-tubulin in non-small cell lung cancer patients treated with carboplatin and paclitaxel. Lung Cancer 2009, 64:326-333.
- [11]Burkhart CA, Kavallaris M, Band Horwitz S: The role of beta-tubulin isotypes in resistance to antimitotic drugs. Biochim Biophys Acta 2001, 1471:O1-O9.
- [12]Crino L, Weder W, van Meerbeeck J, Felip E: Early stage and locally advanced (non-metastatic) non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010, 21(Suppl 5):v103-v115.
- [13]Gossage L, Madhusudan S: Current status of excision repair cross complementing-group 1 (ERCC1) in cancer. Cancer Treat Rev 2007, 33:565-577.
- [14]Li J-J, Ding Y, Li D-D, Peng R-Q, Feng G-K, Zeng Y-X, Zhu X-F, Zhang X-S: The overexpression of ERCC-1 is involved in the resistance of lung cancer cells to cetuximab combined with DDP. Cancer Biol Ther 2009, 8:1914-1921.
- [15]Li J, Li ZN, Yu LC, Bao QL, Wu JR, Shi SB, Li XQ: Association of expression of MRP1, BCRP, LRP and ERCC1 with outcome of patients with locally advanced non-small cell lung cancer who received neoadjuvant chemotherapy. Lung Cancer 2010, 69:116-122.
- [16]Wang X, Zhao J, Yang L, Mao L, An T, Bai H, Wang S, Liu X, Feng G, Wang J: Positive expression of ERCC1 predicts a poorer platinum-based treatment outcome in Chinese patients with advanced non-small-cell lung cancer. Medical Oncology 2010, 27:484-490.
- [17]Cobo M, Isla D, Massuti B, Montes A, Sanchez JM, Provencio M, Vinolas N, Paz-Ares L, Lopez-Vivanco G, Munoz MA, et al.: Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: a phase III trial in non-small-cell lung cancer. J Clin Oncol 2007, 25:2747-2754.
- [18]Zheng Z, Chen T, Li X, Haura E, Sharma A, Bepler G: DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer. N Engl J Med 2007, 356:800-808.
- [19]Lee KH, Min HS, Han SW, Oh DY, Lee SH, Kim DW, Im SA, Chung DH, Kim YT, Kim TY, et al.: ERCC1 expression by immunohistochemistry and EGFR mutations in resected non-small cell lung cancer. Lung Cancer 2008, 60:401-407.
- [20]Ota S, Ishii G, Goto K, Kubota K, Kim YH, Kojika M, Murata Y, Yamazaki M, Nishiwaki Y, Eguchi K, Ochiai A: Immunohistochemical expression of BCRP and ERCC1 in biopsy specimen predicts survival in advanced non-small-cell lung cancer treated with cisplatin-based chemotherapy. Lung Cancer 2009, 64:98-104.
- [21]Cutress RI, Townsend PA, Brimmell M, Bateman AC, Hague A, Packham G: BAG-1 expression and function in human cancer. Br J Cancer 2002, 87:834-839.
- [22]Takayama S, Reed JC: Molecular chaperone targeting and regulation by BAG family proteins. Nat Cell Biol 2001, 3:E237-E241.
- [23]Liu H, Bai Y, Liu B, Wang Z, Wang M, Zhou Q, Chen J: The expression of BAG-1 and its clinical significance in human lung cancer. Zhongguo Fei Ai Za Zhi 2008, 11:489-494.
- [24]Rorke S, Murphy S, Khalifa M, Chernenko G, Tang SC: Prognostic significance of BAG-1 expression in nonsmall cell lung cancer. Int J Cancer 2001, 95:317-322.
- [25]Taron M, Rosell R, Felip E, Mendez P, Souglakos J, Ronco MS, Queralt C, Majo J, Sanchez JM, Sanchez JJ, Maestre J: BRCA1 mRNA expression levels as an indicator of chemoresistance in lung cancer. Hum Mol Genet 2004, 13:2443-2449.
- [26]Quinn JE, James CR, Stewart GE, Mulligan JM, White P, Chang GKF, Mullan PB, Johnston PG, Wilson RH, Harkin DP: BRCA1 mRNA Expression Levels Predict for Overall Survival in Ovarian Cancer after Chemotherapy. Clin Cancer Res 2007, 13:7413-7420.
- [27]Bartolucci R, Wei J, Sanchez JJ, Perez-Roca L, Chaib I, Puma F, Farabi R, Mendez P, Roila F, Okamoto T, et al.: XPG mRNA expression levels modulate prognosis in resected non-small-cell lung cancer in conjunction with BRCA1 and ERCC1 expression. Clin Lung Cancer 2009, 10:47-52.
- [28]Rosell R, Perez-Roca L, Sanchez JJ, Cobo M, Moran T, Chaib I, Provencio M, Domine M, Sala MA, Jimenez U, et al.: Customized treatment in non-small-cell lung cancer based on EGFR mutations and BRCA1 mRNA expression. PLoS One 2009, 4:e5133.
- [29]Kim D, Jung W, Koo JS: The expression of ERCC1, RRM1, and BRCA1 in breast cancer according to the immunohistochemical phenotypes. J Korean Med Sci 2011, 26:352-359.
- [30]Su C, Zhou S, Zhang L, Ren S, Xu J, Zhang J, Lv M, Zhou C: ERCC1, RRM1 and BRCA1 mRNA expression levels and clinical outcome of advanced non-small cell lung cancer. Med Oncol 2010, 28:1411-1417.
- [31]Pitterle DM, Kim YC, Jolicoeur EM, Cao Y, O'Briant KC, Bepler G: Lung cancer and the human gene for ribonucleotide reductase subunit M1 (RRM1). Mamm Genome 1999, 10:916-922.
- [32]Davidson JD, Ma L, Flagella M, Geeganage S, Gelbert LM, Slapak CA: 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 2004, 64:3761-3766.
- [33]Liu B, Staren ED, Iwamura T, Appert HE, Howard JM: Mechanisms of taxotere-related drug resistance in pancreatic carcinoma. J Surg Res 2001, 99:179-186.
- [34]Gan PP, Pasquier E, Kavallaris M: Class III beta-tubulin mediates sensitivity to chemotherapeutic drugs in non small cell lung cancer. Cancer Res 2007, 67:9356-9363.
- [35]Koh Y, Jang B, Han SW, Kim TM, Oh DY, Lee SH, Kang CH, Kim DW, Im SA, Chung DH, et al.: Expression of class III beta-tubulin correlates with unfavorable survival outcome in patients with resected non-small cell lung cancer. J Thorac Oncol 2010, 5:320-325.