Expression of Thymidylate Synthase, Excision Repair Cross-complementing Gene 1, β-tubulin 3 and Ribonucleotide Reductase Subunit 1 in Non-small Cell Lung Cancer and Their Clinical Significance_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

WUBing-qun , LIUMing-liang , DUANXin-chun ,  CUIYong

Department of Thoracic Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P. R. China;

Corresponding author：

CUIYong, Email: cywork1@sina.com

Keywords：

Non-small cell lung cancer; Gene expression; Adjuvant chemotherapy

DOI：

10.7507/1007-4848.20140233

Video：

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Objective To investigate expression levels of thymidylate synthase (TS), excision repair cross-comple-menting gene 1 (ERCC1), β-tubulin 3 (TUBB3), ribonucleotide reductase subunit 1 (RRM1)in different pathological types of non-small cell lung cancer (NSCLC), and evaluate detection strategies of above genes for individualized chemotherapy of NSCLC. Methods We retrospectively analyzed clinical data of 94 NSCLC patients who underwent radical resection in Department of Thoracic Surgery of Beijing Friendship Hospital from February 2010 to October 2012. Messenger ribonu-cleic acid (mRNA)expression levels of TS, ERCC1, TUBB3 and RRM1 were examined by immunohistochemistry. Results There were 91 patients (96.81%)with low mRNA expression of TS, 90 patients (95.74%)with low mRNA expression of ERCC1, 59 patients (62.77%)with low mRNA expression of TUBB3, and 48 patients (51.06%)with low mRNA expression of RRM1. There was no statistical difference in mRNA expression levels of TS, ERCC1, TUBB3 or RRM1 between adenocarcinoma and non-adenocarcinomas (P > 0.05). The percentage of low mRNA expression of TUBB3 in adenocarcinoma was significantly lower than that in non-adenocarcinomas (58.21% vs. 74.07%). Among patients with same pathological types of NSCLC, mRNA expression levels of TS, ERCC1 and TUBB3 were all positively correlated with mRNA expression of RRM1 (correlation coefficient all greater than 0.80). Conclusion For individualized chemotherapy of NSCLC, when selecting gene detection, mRNA expression levels of ERCC1 and TS need not be detected and can be considered as low expression by experience, mRNA expression levels of TUBB3 in adenocarcinoma and RRM1 in all pathological types of NSCLC should be routinely examined. For non-adenocarcinoma patients, whether or not to examine mRNA expression level of TUBB3 can be decided in a comprehensive manner.

Citation： WUBing-qun, LIUMing-liang, DUANXin-chun, CUIYong. Expression of Thymidylate Synthase, Excision Repair Cross-complementing Gene 1, β-tubulin 3 and Ribonucleotide Reductase Subunit 1 in Non-small Cell Lung Cancer and Their Clinical Significance. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2014, 21(6): 813-816. doi: 10.7507/1007-4848.20140233 Copy

1.	Jemal A, Siegel R, Ward E, et al. Cancer statistics. CA Cancer J Clin, 2008, 58(2):71-96.
2.	Jemal A, Bray F, Center MM, et al. Global Cancer statistics. CA Cancer J Clin, 2011, 61(2):69-90.
3.	Wei HB, Lu XS, Shang LH, et al. Polymorphisms of ERCC1 C118T/C8092A and MDR1 C3435T predict outcome of platinum-based chemotherapies in advanced non-small cell lung cancer:a meta-analysis. Arch Med Res, 2011, 42(5):412-420.
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11.	Wang X, Wang Y, Wang Y, et al. Association of thymidylate synthase gene 3'-untranslated region polymorphism with sensitivity of non-small celllung cancer to pemetrexed treatment:TS gene polymorphism and pemetrexed sensitivity in NSCLC. J Biomed Sci, 2013, 20:5.
12.	Shimizu T, Nakanishi Y, Nakagawa Y, et al. Association between expression of thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase and efficacy of pemetrexed in advanced non-small cell lung cancer. Anticancer Res, 2012, 32(10):4589-4596.
13.	Sun JM, Han J, Ahn JS, et al. Significance of thymidylate synthase and thyroid transcription factor 1 expression in patients with nonsquamous non-small cell lung cancer treated with pemetrexed-based chemotherapy. J Thorac Oncol, 2011, 6(8):1392-1399.
14.	Hu Q, Li X, Su C, et al. Correlation between thymidylate synthase gene polymorphisms and efficacy of pemetrexed in advanced non-small cell lung cancer. Exp Ther Med, 2012, 4(6):1010-1016.
15.	潘泓, 左传田, 李力, 等. RNA干扰抑制ERCC1基因对肺癌细胞A549药物敏感性影响的研究.中华肿瘤防治杂志, 2009, 16(14):1059-1061.
16.	Olaussen KA, Dunant A, Fouret P, et al. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemother-apy. N Engl J Med, 2006, 355(10):983-991.
17.	Cobo M, Isla D, Massuti B, et al. Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression:a phase Ⅲ trial in non-small-cell lung cancer. Clin Oncol, 2007, 25(19):2747-2754.
18.	Cheng J, Ha M, Wang Y, et al. A C118T polymorphism of ERCC1 and response to cisplatin chemotherapy in patients with late-stage non-small cell lung cancer. Cancer Res Clin Oncol, 2012, 138(2):231-238.
19.	Xiao H, Verdier P, Fernandez N, et al. Insights into the mechanism of microtubule stabilization by taxol. Proc Nat l Acad Sci, 2006, 103(27):10166-10173.
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21.	Vilmar AC, Santoni-Rugiu E, Sørensen JB. Class Ⅲ β-tubulin in advanced NSCLC of adenocarcinoma subtype predicts superior outcome in a randomizedtrial. Clin Cancer Res, 2011, 17(15):5205-5214.
22.	Zhang GB, Chen J, Wang LR, et al. Expression of RRM1 and ERCC1 genes in tumor tissues and peripheral blood lymphocytes of advanced non-small cell lung cancer. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2012, 41(5):540-546.
23.	Wang LR, Zhang GB, Chen J, et al. RRM1 gene expression in peripheral blood is predictive of shorter. J Zhejiang Univ Sci B, 2011, 12(3):174-179.
24.	Lee JJ, Maeng CH, Baek SK, et al. 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, 2010, 70(2):205-210.
25.	Jian-Wei B, Yi-Min M, Yu-Xia S, et al. Expression levels of ERCC1 and RRM1 mRNA and clinical outcome of advanced non-small cell lung cancer. Pak J Med Sci, 2013, 29(5):1158-1161.

1. Jemal A, Siegel R, Ward E, et al. Cancer statistics. CA Cancer J Clin, 2008, 58(2):71-96.
2. Jemal A, Bray F, Center MM, et al. Global Cancer statistics. CA Cancer J Clin, 2011, 61(2):69-90.
3. Wei HB, Lu XS, Shang LH, et al. Polymorphisms of ERCC1 C118T/C8092A and MDR1 C3435T predict outcome of platinum-based chemotherapies in advanced non-small cell lung cancer:a meta-analysis. Arch Med Res, 2011, 42(5):412-420.
4. 尹迎春, 王新美, 王新云, 等.四甲基偶氮唑盐体外药物敏感试验联合多药耐药基因1检测预测非小细胞肺癌的化疗敏感性.中国胸心血管外科临床杂志, 2012, 19(5):547-550.
5. Korpanty G, Smyth E, Carney DN. Update on anti-angiogenic therapy in non-small cell lung cancer:Are we making progress? Thorac Dis, 2011, 3(1):19-29.
6. 王磊, 侯生才, 李辉, 等.血清肝细胞生长因子及转化生长因子-β水平在非小细胞肺癌患者术前分期中的意义.中国胸心血管外科临床杂志, 2010, 17(6):462-466.
7. 王波, 王彬, 张连斌, 等. TUBB3/STMN1基因表达与非小细胞肺癌EGFR通路的相关性.中国肺癌杂志, 2013, 16(10):547-552.
8. Jemal A1, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J Clin, 2010, 60(5):277-300.
9. 方勇, 倪旭东. CT引导射频消融治疗非小细胞肺癌的临床分析.中国胸心血管外科临床杂志, 2013, 20(4):479-481.
10. Peterson P, Park K, Fossella F, et al. Is pemetrexed more effective in adenocarcinoma and large cell lung cancer than in squamous cell carcinoma? A retrospective analysis of a phase Ⅲ trial of pemetrexed vs docetaxel in previously treated patients with advanced nonsmall cell lung cancer. Thor Oncol, 2007, 2(8 Suppl 4):s851.
11. Wang X, Wang Y, Wang Y, et al. Association of thymidylate synthase gene 3'-untranslated region polymorphism with sensitivity of non-small celllung cancer to pemetrexed treatment:TS gene polymorphism and pemetrexed sensitivity in NSCLC. J Biomed Sci, 2013, 20:5.
12. Shimizu T, Nakanishi Y, Nakagawa Y, et al. Association between expression of thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase and efficacy of pemetrexed in advanced non-small cell lung cancer. Anticancer Res, 2012, 32(10):4589-4596.
13. Sun JM, Han J, Ahn JS, et al. Significance of thymidylate synthase and thyroid transcription factor 1 expression in patients with nonsquamous non-small cell lung cancer treated with pemetrexed-based chemotherapy. J Thorac Oncol, 2011, 6(8):1392-1399.
14. Hu Q, Li X, Su C, et al. Correlation between thymidylate synthase gene polymorphisms and efficacy of pemetrexed in advanced non-small cell lung cancer. Exp Ther Med, 2012, 4(6):1010-1016.
15. 潘泓, 左传田, 李力, 等. RNA干扰抑制ERCC1基因对肺癌细胞A549药物敏感性影响的研究.中华肿瘤防治杂志, 2009, 16(14):1059-1061.
16. Olaussen KA, Dunant A, Fouret P, et al. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemother-apy. N Engl J Med, 2006, 355(10):983-991.
17. Cobo M, Isla D, Massuti B, et al. Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression:a phase Ⅲ trial in non-small-cell lung cancer. Clin Oncol, 2007, 25(19):2747-2754.
18. Cheng J, Ha M, Wang Y, et al. A C118T polymorphism of ERCC1 and response to cisplatin chemotherapy in patients with late-stage non-small cell lung cancer. Cancer Res Clin Oncol, 2012, 138(2):231-238.
19. Xiao H, Verdier P, Fernandez N, et al. Insights into the mechanism of microtubule stabilization by taxol. Proc Nat l Acad Sci, 2006, 103(27):10166-10173.
20. Zhang HL, Ruan L, Zheng LM, et al. Association between class Ⅲ beta-tubulin expression and response to paclitaxel/vinorebine-based chemotherapy for non-small cell lung cancer:A meta-analysis. Lung Cancer, 2012, 77(1):9-15.
21. Vilmar AC, Santoni-Rugiu E, Sørensen JB. Class Ⅲ β-tubulin in advanced NSCLC of adenocarcinoma subtype predicts superior outcome in a randomizedtrial. Clin Cancer Res, 2011, 17(15):5205-5214.
22. Zhang GB, Chen J, Wang LR, et al. Expression of RRM1 and ERCC1 genes in tumor tissues and peripheral blood lymphocytes of advanced non-small cell lung cancer. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2012, 41(5):540-546.
23. Wang LR, Zhang GB, Chen J, et al. RRM1 gene expression in peripheral blood is predictive of shorter. J Zhejiang Univ Sci B, 2011, 12(3):174-179.
24. Lee JJ, Maeng CH, Baek SK, et al. 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, 2010, 70(2):205-210.
25. Jian-Wei B, Yi-Min M, Yu-Xia S, et al. Expression levels of ERCC1 and RRM1 mRNA and clinical outcome of advanced non-small cell lung cancer. Pak J Med Sci, 2013, 29(5):1158-1161.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Expression of Thymidylate Synthase, Excision Repair Cross-complementing Gene 1, β-tubulin 3 and Ribonucleotide Reductase Subunit 1 in Non-small Cell Lung Cancer and Their Clinical Significance

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