Advertisement

Tumor Biology

, Volume 35, Issue 12, pp 12707–12712 | Cite as

ERCC1 and the efficacy of cisplatin in patients with resected non-small cell lung cancer

Research Article

Abstract

Excision repair cross-complementing gene 1 (ERCC1) protein is proposed as a predictor for cisplatin efficacy in patients with non-small cell lung cancer (NSCLC). However, recent studies declare that ERCC1 is not associated with the response of platinum-based chemotherapy or clinical outcomes. The purpose of this study is to assess whether ERCC1 expression level is linked to cisplatin sensitivity and clinical outcomes in resected NSCLC patients. Paraffin-embedded cancer samples from 112 patients were used for immunohistochemical staining. Cancer cells isolated from fresh tumor tissues were used to determine the sensitivity to cisplatin by MTT assay. The association between ERCC1 expression and cisplatin sensitivity was tested by Spearman’s rho test. The correlation of ERCC1 expression with clinicopathologic parameters was evaluated by the chi-square tests. The relationship between variables and survival was assessed by log-rank test. Overall survival (OS) and disease-free survival (DFS) curves were plotted by the Kaplan–Meier method. Cox proportional hazards model was used for multivariate analysis of survival. ERCC1 expression was significantly correlated with the sensitivity of cisplatin in vitro (p < 0.01, r = 0.37). ERCC1 was not associated with OS (p = 0.17) or DFS (p = 0.13) in patients with resected NSCLC. ERCC1 is not a sensible marker for the choice of treatment in clinical patients with resected NSCLC.

Keywords

Non-small cell lung cancer (NSCLC) Excision repair cross-complementing gene 1 (ERCC1) Survival Cisplatin 

Notes

Acknowledgments

This study was supported by Harbin Medical University Cancer Hospital (Grant JJZ2011-02) and National Natural Science Foundation of China (Grant 30772540).

Conflicts of interest

None

References

  1. 1.
    Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, et al. Cancer treatment and survivorship statistics, 2012. CA. 2012;62:220–41.PubMedGoogle Scholar
  2. 2.
    Siegel R, Naishadham D, Jemal A. Cancer statistics. CA Cancer J Clin. 2012;62:10–29.PubMedCrossRefGoogle Scholar
  3. 3.
    Team TNLSTR. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395–409.CrossRefGoogle Scholar
  4. 4.
    Yang G, Wang Y, Zeng Y, Gao GF, Liang X, Zhou M, et al. Rapid health transition in China, 1990–2010: findings from the Global Burden of Disease Study 2010. Lancet. 2013;V381N9882:1987–2015.CrossRefGoogle Scholar
  5. 5.
    Saisho S, Yasuda K, Maeda A, Yukawa T, Okita R, Hirami Y, et al. Post-recurrence survival of patients with non-small-cell lung cancer after curative resection with or without induction/adjuvant chemotherapy. Interact Cardiovasc Thorac Surg. 2013;16(2):166–72.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Booth CM, Shepherd FA, Peng Y, Darling G, Li G, Kong W, et al. Time to adjuvant chemotherapy and survival in non-small cell lung cancer: a population-based study. Cancer. 2013;119(6):1243–50.PubMedCrossRefGoogle Scholar
  7. 7.
    Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J. International Adjuvant Lung Cancer Trial Collaborative G: cisplatin-based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. N Engl J Med. 2004;350(4):351–60.PubMedCrossRefGoogle Scholar
  8. 8.
    Alam N, Shepherd FA, Winton T, Graham B, Johnson D, Livingston R, et al. Compliance with post-operative adjuvant chemotherapy in non-small cell lung cancer. An analysis of National Cancer Institute of Canada and intergroup trial JBR.10 and a review of the literature. Lung Cancer. 2005;47:385–94.PubMedCrossRefGoogle Scholar
  9. 9.
    Simon GR, Ismail-Khan R, Bepler G. Nuclear excision repair-based personalized therapy for non-small cell lung cancer: from hypothesis to reality. Int J Biochem Cell Biol. 2007;39:1318–28.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Maus MK, Mack PC, Astrow SH, Stephens CL, Zeger GD, Grimminger PP, et al. Histology-related associations of ERCC1, RRM1, and TS biomarkers in patients with non-small-cell lung cancer: implications for therapy. J Thorac Oncol. 2013;8:582–6.PubMedGoogle Scholar
  11. 11.
    Zhang GB, Chen J, Wang LR, Li J, Li MW, Xu N, et al. RRM1 and ERCC1 expression in peripheral blood versus tumor tissue in gemcitabine/carboplatin-treated advanced non-small cell lung cancer. Cancer Chemother Pharmacol. 2012;69:1277–87.PubMedCrossRefGoogle Scholar
  12. 12.
    Olaussen KA, Dunant A, Fouret P, Brambilla E, André F, Haddad V, et al. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med. 2006;355:983–91.PubMedCrossRefGoogle Scholar
  13. 13.
    Volker M, Moné MJ, Karmakar P, van Hoffen A, Schul W, Vermeulen W, et al. Sequential assembly of the nucleotide excision repair factors in vivo. Mol Cell. 2001;8:213–24.PubMedCrossRefGoogle Scholar
  14. 14.
    Yu D, Shi J, Sun T, Du X, Liu L, Zhang X, et al. Pharmacogenetic role of ERCC1 genetic variants in treatment response of platinum-based chemotherapy among advanced non-small cell lung cancer patients. Tumour Biol. 2012;33:877–84.PubMedCrossRefGoogle Scholar
  15. 15.
    Sodja E, Knez L, Kern I, Ovčariček T, Sadikov A, Cufer T. Impact of ERCC1 expression on treatment outcome in small-cell lung cancer patients treated with platinum-based chemotherapy. Eur J Cancer. 2012;48:3378–85.PubMedCrossRefGoogle Scholar
  16. 16.
    Ota S, Ishii G, Goto K, Kubota K, Kim YH, Kojika M, et al. 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.PubMedCrossRefGoogle Scholar
  17. 17.
    Tantraworasin A, Saeteng S, Lertprasertsuke N, Arayawudhikul N, Kasemsarn C, Patumanond J. The prognostic value of ERCC1 and RRM1 gene expression in completely resected non-small cell lung cancer: tumor recurrence and overall survival. Cancer Manag Res. 2013;5:327–36.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Pesta M, Kulda V, Fiala O, Safranek J, Topolcan O, Krakorova G, et al. Prognostic significance of ERCC1, RRM1 and BRCA1 in surgically-treated patients with non-small cell lung cancer. Anticancer Res. 2012;32:5003–10.PubMedGoogle Scholar
  19. 19.
    Zhou W, Gurubhagavatula S, Liu G, Park S, Neuberg DS, Wain JC, et al. Excision repair cross-complementation group 1 polymorphism predicts overall survival in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy. Clin Cancer Res. 2004;10:4939–43.PubMedCrossRefGoogle Scholar
  20. 20.
    Kelly K, Crowley J, Bunn Jr PA, Presant CA, Grevstad PK, Moinpour CM, et al. Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non–small-cell lung cancer: a Southwest Oncology Group trial. J Clin Oncol. 2001;19:3210–8.PubMedGoogle Scholar
  21. 21.
    Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002;346:92–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Fossella F, Pereira JR, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, et al. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003;21:1–9.CrossRefGoogle Scholar
  23. 23.
    Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129–39.PubMedCrossRefGoogle Scholar
  24. 24.
    Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304:1497–500.PubMedCrossRefGoogle Scholar
  25. 25.
    Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363:1693–703.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Friboulet L, Olaussen KA, Pignon JP, Shepherd FA, Tsao MS, Graziano S, et al. ERCC1 isoform expression and DNA repair in non-small-cell lung cancer. N Engl J Med. 2013;368:1101–10.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Reynolds C, Obasaju C, Schell MJ, Li X, Zheng Z, Boulware D, et al. Randomized phase III trial of gemcitabine-based chemotherapy with in situ RRM1 and ERCC1 protein levels for response prediction in non-small-cell lung cancer. J Clin Oncol. 2009;27:5808–15.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Cobo M, Isla D, Massuti B, Montes A, Sanchez JM, Provencio M, et al. Customizing cisplatin based on quantitative excision repair crosscomplementing 1 mRNA expression: a phase III trial in non-small-cell lung cancer. J Clin Oncol. 2007;25:2747–54.PubMedCrossRefGoogle Scholar
  29. 29.
    Simon G, Sharma A, Li X, Hazelton T, Walsh F, Williams C, et al. Feasibility and efficacy of molecular analysis-directed individualized therapy in advanced non-small-cell lung cancer. J Clin Oncol. 2007;25:2741–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Lord RV, Brabender J, Gandara D, Alberola V, Camps C, Domine M, et al. Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res. 2002;8:2286–91.PubMedGoogle Scholar
  31. 31.
    Vassalou H, Stathopoulos E, Fiolitaki G, Koutsopoulos A, Voutsina A, Georgoulias V, et al. Excision-repair-cross-complement-1 protein as a prognostic factor in patients with advanced non-small cell lung cancer treated with platinum-based first-line chemotherapy. Lung Cancer. 2013;82:324–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Bepler G, Kusmartseva I, Sharma S, Gautam A, Cantor A, Sharma A, et al. RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer. J Clin Oncol. 2006;24:4731–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Ceppi P, Volante M, Novello S, Rapa I, Danenberg KD, Danenberg PV, et al. 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. 2006;17:1818–25.PubMedCrossRefGoogle Scholar
  34. 34.
    Bepler G, Williams C, Schell MJ, Chen W, Zheng Z, Simon G, et al. Randomized international phase III trial of ERCC1 and RRM1 expression-based chemotherapy versus gemcitabine/carboplatin in advanced non-small-cell lung cancer. J Clin Oncol. 2013;1(31):2404–12.CrossRefGoogle Scholar
  35. 35.
    Zheng Z, Chen T, Li X, Haura E, Sharma A, Bepler G. The DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer. N Engl J Med. 2007;356:800–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Toffart AC, Timsit JF, Couraud S, Merle P, Moro-Sibilot D, Perol M, et al. Immunohistochemistry evaluation of biomarker expression in non-small cell lung cancer (Pharmacogenoscan study). Lung Cancer. 2013 Dec 21.Google Scholar
  37. 37.
    Booton R, Ward T, Ashcroft L, Morris J, Heighway J, Thatcher N. ERCC1 mRNA expression is not associated with response and survival after platinum-based chemotherapy regimens in advanced non-small cell lung cancer. J Thorac Oncol. 2007;2:902–6.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of Internal Medical OncologyHarbin Medical University Cancer HospitalHarbinPeople’s Republic of China
  2. 2.Department of Biomedical and Pharmaceutical Sciences, College of PharmacyThe University of Rhode IslandKingstonUSA
  3. 3.Department of Internal Medicine College of MedicineThe University of Oklahoma Health Sciences CenterOklahoma CityUSA

Personalised recommendations