Tumor Biology

, Volume 35, Issue 5, pp 4697–4704 | Cite as

ERCC1 and BRCA1 mRNA expressions are associated with clinical outcome of non-small cell lung cancer treated with platinum-based chemotherapy

  • Xiuguang Qin
  • Wenjian Yao
  • Weiwei Li
  • Xianjun Feng
  • Xiaoqing Huo
  • Shujuan Yang
  • Hui Zhao
  • Xiaomeng Gu
Research Article


We conducted a perspective study to investigate whether the expression of excision repair cross-complementing 1 (ERCC1), xeroderma pigmentosum group G (XPG), breast cancer 1 (BRCA1), and ribonucleotide reductase M1 (RRM1) is correlated with clinical outcome of non-small cell lung cancer (NSCLC). Patients with histologically confirmed inoperable stages IIIB and IV NSCLC were collected and followed up until January 2012. Relative cDNA quantification for ERCC1, XPG, BRCA1, and RRM1 was performed using a fluorescence-based, real-time detection method. Cox regression analysis indicated that a high level of ERCC1 was associated with shorter overall survival (OS) and progression-free survival (PFS) times when compared with low expression, with adjusted hazard ratios (HRs) (95 % confidence interval (CI)) of 2.25 (1.18–4.39) and 2.63 (1.33–5.25), respectively. High expression of BRCA1 was correlated with shorter OS and PFS times when compared with low expression, and the adjusted HRs (95 % CI) were 3.29 (1.72–6.39) and 5.94 (2.80–13.06), respectively. Moreover, we found a significant correlation between BRCA1 expression and age (χ 2 = 4.14, P = 0.04) and stage (χ 2 = 5.26, P = 0.02). Our results suggest that ERCC1 and BRCA1 mRNA expressions are associated with PFS and OS in advanced NSCLC patients treated with platinum-based chemotherapy.


ERCC1 BRCA1 mRNA Non-small cell lung cancer Platinum-based chemotherapy Clinical outcome 



We thank the staffs of the First Affiliated Hospital of Xinxiang Medical University for their help and patients who agreed to provide blood samples.

Conflicts of interest



  1. 1.
    International Agency for Research on Cancer. Globocan 2008: Lung cancer incidence, mortality and prevalence worldwide in 2008. Summary.
  2. 2.
    Bartolucci R, Wei J, Sanchez JJ, Perez-Roca L, Chaib I, Puma F, 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(1):47–52.CrossRefPubMedGoogle Scholar
  3. 3.
    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(11):5003–10.PubMedGoogle Scholar
  4. 4.
    Su C, Zhou S, Zhang L, Ren S, Xu J, Zhang J, et al. ERCC1, RRM1 and BRCA1 mRNA expression levels and clinical outcome of advanced non-small cell lung cancer. Med Oncol. 2011;28(4):1411–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Bidoli P, Zilembo N, Cortinovis D, Mariani L, Isa L, Aitini E, et al. Randomized phase II three-arm trial with three platinum-based doublets in metastatic nonsmall-cell lung cancer. An Italian Trials in Medical Oncology Study. Ann Oncol. 2007;18:461–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Vilmar A, Sorensen JB. Excision repair cross-complementation group 1 (ERCC1) in platinum-based treatment of non-small cell lung cancer with special emphasis on carboplatin: a review of current literature. Lung Cancer. 2009;64:131–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Johnson DH. Gemcitabine for the treatment of non-small-cell lung cancer. Oncology (Williston Park). 2001;15(3 Suppl 6):33–9.Google Scholar
  8. 8.
    Jordan P, Carmo-Fonseca M. Molecular mechanisms involved in cisplatin cytotoxicity. Cell Mol Life Sci. 2000;57(8–9):1229–35.CrossRefPubMedGoogle Scholar
  9. 9.
    van de Vaart PJ, Belderbos J, de Jong D, Sneeuw KC, Majoor D, Bartelink H, et al. DNA-adduct levels as a predictor of outcome for NSCLC patients receiving daily cisplatin and radiotherapy. Int J Cancer. 2000;89(2):160–6.CrossRefPubMedGoogle Scholar
  10. 10.
    Cai Y, Geacintov NE, Broyde S. Nucleotide excision repair efficiencies of bulky carcinogen-DNA adducts are governed by a balance between stabilizing and destabilizing interactions. Biochemistry. 2012;51(7):1486–99.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Sugasawa K. Xeroderma pigmentosum genes: functions inside and outside DNA repair. Carcinogenesis. 2008;29:455–65.CrossRefPubMedGoogle Scholar
  12. 12.
    Taron M, Rosell R, Felip E, et al. BRCA1 mRNA expression levels as an indicator of chemoresistance in lung cancer. Hum Mol Genet. 2004;13:2443–9.CrossRefPubMedGoogle Scholar
  13. 13.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Liao WY, Shih JY, Chang GC, Cheng YK, Yang JC, Chen YM, et al. Genetic polymorphism of XRCC1 Arg399Gln is associated with survival in non-small-cell lung cancer patients treated with gemcitabine/platinum. J Thorac Oncol. 2012;7(6):973–81.CrossRefPubMedGoogle Scholar
  15. 15.
    Tiseo M, Bordi P, Bortesi B, Boni L, Boni C, Baldini E, et al. Bio-FAST trial group. ERCC1/BRCA1 expression and gene polymorphisms as prognostic and predictive factors in advanced NSCLC treated with or without cisplatin. Br J Cancer. 2013;108(8):1695–703.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Leng XF, Chen MW, Xian L, Dai L, Ma GY, Li MH. 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. J Exp Clin Cancer Res. 2012;31:25.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Vilmar A, Garcia-Foncillas J, Huarriz M, Santoni-Rugiu E, Sorensen JB. RT-PCR versus immunohistochemistry for correlation and quantification of ERCC1, BRCA1, TUBB3 and RRM1 in NSCLC. Lung Cancer. 2012;75(3):306–12.CrossRefPubMedGoogle Scholar
  18. 18.
    Wei J, Zou ZY, Qian XP, Wang LF, Yu LX, Liu BR. ERCC1 mRNA expression levels and outcome of gastric cancer patients receiving oxaliplatin-based chemotherapy. Zhonghua Bing Li Xue Za Zhi. 2008;37(8):551–2.PubMedGoogle Scholar
  19. 19.
    Bai ZL, Wang YY, Zhe H, He JL, Hai P. ERCC1 mRNA levels can predict the response to cisplatin-based concurrent chemoradiotherapy of locally advanced cervical squamous cell carcinoma. Radiat Oncol. 2012;7:221.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Baba H, Watanabe M, Okabe H, Miyamoto Y, Sakamoto Y, Baba Y, et al. Upregulation of ERCC1 and DPD expressions after oxaliplatin-based first-line chemotherapy for metastatic colorectal cancer. Br J Cancer. 2012;107(12):1950–5.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Liu GY, Qu QX, Mi RR, Qi J. Relationship between nucleotide excision repair gene ERCC1 and resistance to cisplatin in ovarian cancer. Zhonghua Zhong Liu Za Zhi. 2008;30(3):184–7.PubMedGoogle Scholar
  22. 22.
    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;31(19):2404–12.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Papadaki C, Sfakianaki M, Ioannidis G, Lagoudaki E, Trypaki M, Tryfonidis K, et al. ERCC1 and BRAC1 mRNA expression levels in the primary tumor could predict the effectiveness of the second-line cisplatin-based chemotherapy in pretreated patients with metastatic non-small cell lung cancer. J Thorac Oncol. 2012;7(4):663–71.CrossRefPubMedGoogle Scholar
  24. 24.
    Chen S, Zhang J, Wang R, et al. The platinum-based treatments for advanced non-small cell lung cancer, is low/negative ERCC1 expression better than high/positive ERCC1 expression? A meta-analysis. Lung Cancer. 2010;70:63–70.CrossRefPubMedGoogle Scholar
  25. 25.
    Quinn JE, Kennedy RD, Mullan PB, Gilmore PM, Carty M, et al. BRCA1 functions as a differential modulator of chemotherapy-induced apoptosis. Cancer Res. 2003;63:6221–8.PubMedGoogle Scholar
  26. 26.
    Han Y, Wang XB, Xiao N, Liu ZD. mRNA expression and clinical significance of ERCC1, BRCA1, RRM1, TYMS and TUBB3 in postoperative patients with non-small cell lung cancer. Asian Pac J Cancer Prev. 2013;14(5):2987–90.CrossRefPubMedGoogle Scholar
  27. 27.
    Wang L, Meng L, Wang XW, Ma GY, Chen JH. Expression of RRM1 and RRM2 as a novel prognostic marker in advanced non-small cell lung cancer receiving chemotherapy. Tumour Biol. 2013.Google Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Xiuguang Qin
    • 1
  • Wenjian Yao
    • 1
  • Weiwei Li
    • 2
  • Xianjun Feng
    • 3
  • Xiaoqing Huo
    • 2
  • Shujuan Yang
    • 4
  • Hui Zhao
    • 5
  • Xiaomeng Gu
    • 6
  1. 1.Department of Thoracic SurgeryThe First Affiliated Hospital of Xinxiang Medical UniversityWeihuiChina
  2. 2.Oncology DepartmentThe First Affiliated Hospital of Xinxiang Medical UniversityWeihuiChina
  3. 3.Department of Respiratory MedicineThe First Affiliated Hospital of Xinxiang Medical UniversityWeihuiChina
  4. 4.Department of Health and Social Behavior, West China School of Public HealthSichuan UniversityChengduChina
  5. 5.Department of Thoracic Surgery, Qilu HospitalShandong UniversityJinanChina
  6. 6.Department of Gastroenterology, Qilu HospitalShandong UniversityJinanChina

Personalised recommendations