Tumor Biology

, Volume 35, Issue 5, pp 4499–4507 | Cite as

Survivin mRNA-circulating tumor cells predict treatment efficacy of chemotherapy and survival for advanced non-small cell lung cancer patients

  • Yong-Jie Du
  • Jian Li
  • Wen-Fang Zhu
  • Yan Wu
  • Xin-Ping Tang
  • Yi Wang
  • Yi-Ming Hu
Research Article

Abstract

The purpose of this prospective study was to evaluate the prognostic and predictive value of survivin mRNA-circulating tumor cells (CTCs) in peripheral blood of patients with advanced non-small cell lung cancer (NSCLC) who received first-line chemotherapy. Blood samples were collected from 78 patients with stage IIIB and IV NSCLC before (C0) and after 1 cycle (C1) and 3 cycles (C3) of chemotherapy. Survivin mRNA-CTCs were detected by real-time quantitative-PCR and correlated with treatment response and survival. The results showed that the presence of survivin mRNA-CTCs before and during chemotherapy was associated with histology type, tumor stage, and number of sites of metastasis. Moreover, the detection of survivin mRNA-CTCs after 1 and 3 cycles of chemotherapy was significantly associated with imaging response to treatment. Patients with positivity for survivin mRNA-CTCs at C0, C1, and C3 time points had significantly shorter progressive-free survival (PFS) and overall survival (OS) compared with patients without. Multivariate analysis using a Cox proportional hazards model revealed that the presence of survivin mRNA-CTCs after one and three chemotherapy cycles was a significant independent factor for worse PFS and OS. In conclusion, the detection of survivin mRNA-CTCs before and during chemotherapy is a prognostic and predictive factor correlated with poor PFS and OS in patients with advanced NSCLC.

Keywords

Advanced stage Chemotherapy Circulating tumor cell Non-small cell cancer Prognosis Survivin mRNA 

Notes

Conflicts of interest

None.

References

  1. 1.
    Martins SJ, Pereira JR. Clinical factors and prognosis in non-small cell lung cancer. Am J Clin Oncol. 1999;22:453–7.CrossRefPubMedGoogle Scholar
  2. 2.
    Wakelee H, Belani CP. Optimizing first-line treatment options for patients with advanced NSCLC. Oncologist. 2005;10 suppl 3:1–10.CrossRefPubMedGoogle Scholar
  3. 3.
    Molina JR, Adjei AA, Jett JR. Advances in chemotherapy of non-small cell lung cancer. Chest. 2006;130:1211–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Cristofanilli M, Budd GT, Ellis MJ, et al. Circulating tumor cells, disease progression and survival in metastatic breast cancer. N Engl J Med. 2004;351:781–91.CrossRefPubMedGoogle Scholar
  5. 5.
    Hayes DF, Cristofanilli M, Budd GT, et al. Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin Cancer Res. 2006;15:4218–24.CrossRefGoogle Scholar
  6. 6.
    Cohen SJ, Punt CJ, Iannotti N, et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26:3212–21.Google Scholar
  7. 7.
    De Bono JS, Scher HI, Montgonery RB, et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res. 2008;14:6302–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Danila DC, Heller G, Gignac GA, et al. Circulating tumor cell number and prognosis in progressive castration-resistant prostate cancer. Clin Cancer Res. 2007;13:7053–7.CrossRefPubMedGoogle Scholar
  9. 9.
    Pierge J-Y, Hajage D, Bachelot T, et al. High independent prognostic and predictive value of circulating tumor cells compared with serum tumor markers in a large prospective trial in first-line chemotherapy for metastatic breast cancer patients. Ann Oncol. 2012;23:618–24.CrossRefGoogle Scholar
  10. 10.
    Punnoose EA, Alwal S, Liu W, et al. Evaluation of circulating tumor cells and circulating tumor DNA in non-small cell lung cancer: association with clinical endpoints in a phase II clinical trial of pertuzumaband and erlotinib. Clin Cancer Res. 2012;18:2391–401.CrossRefPubMedGoogle Scholar
  11. 11.
    Ross JS, Slodkowska EA. Circulating and disseminated tumor cells in the management of breast cancer. Am J Clin Pathol. 2009;132:237–45.CrossRefPubMedGoogle Scholar
  12. 12.
    Altieri DC. Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene. 2003;22:8581–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Altieri DC. Validating survivin as a cancer therapeutic target. Nat Rev Cancer. 2003;4:46–54.CrossRefGoogle Scholar
  14. 14.
    Yie S-M, Luo B, Ye N-Y, et al. Detection of survivin-expressing circulating cancer cells in the peripheral blood of breast cancer patients by a RT-PCR ELISA. Clin Exp Metastasis. 2006;23:279–89.CrossRefPubMedGoogle Scholar
  15. 15.
    Cao M, Yie S-M, Mu S-M, et al. Detection of survivin-expressing circulating cancer cells in the peripheral blood of patients with esophageal squamous cell carcinoma and its clinical significance. Clin Exp Metastasis. 2009;26:751–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Yie S-M, Lou B, Ye S-R, et al. Clinical significance of detecting survivin-expressing circulating cancer cells in patients with non-small cell lung cancer. Lung Cancer. 2009;63:284–90.CrossRefPubMedGoogle Scholar
  17. 17.
    Yie S-M, Lou B, Ye S-R, et al. Detection of survivin-expressing circulating cancer cells (CCCs) in peripheral blood of patients with gastric and colorectal cancer reveals high risks of relapse. Ann Surg Oncol. 2008;15:3073–82.CrossRefPubMedGoogle Scholar
  18. 18.
    Therasse P, Arbuck SG, Eisenhauer EA, et al. New guideline to evaluate the response to treatment in solid tumors. J Natl Cancer Inst. 2000;92:205–16.CrossRefGoogle Scholar
  19. 19.
    Tang X-P, Li J, Yu L-C, et al. Clinical significance of survivin and VEGF mRNA detection in the cell fraction of the peripheral blood in non-small cell lung cancer patients before and after surgery. Lung Cancer. 2013;81:273–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Livak KJ, Schimittgen TD. Analysis of reactive gene expression data using real-time quantitative PCR and 2−ΔΔCt method. Method. 2001;25:402–8.CrossRefGoogle Scholar
  21. 21.
    McShane LM, Altman DG, Sauerbrei W, et al. Reporting recommendations for tumor marker prognostic studies (REMARK). Eur J Cancer. 2005;41:1690–6.CrossRefPubMedGoogle Scholar
  22. 22.
    Fukuda S, Pelus LM. Survivin, a cancer target with an emerging role in normal adult tissue. Mol Cancer Ther. 2006;5:1087–98.CrossRefPubMedGoogle Scholar
  23. 23.
    Chen P, Li J, Ge L-P, et al. Prognostic value of survivin, X-linked inhibitor of apoptosis protein and second mitochondria-derived activator of caspases expression in advanced non-small lung cancer patients. Respirology. 2010;15:501–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Dai C-H, Li J, Shi S-B, et al. Survivin and Smac gene expressions but not livin are predictors of prognosis in non-small cell lung cancer patients treated with adjuvant chemotherapy following surgery. Jpn J Clin Oncol. 2010;40:327–35.CrossRefPubMedGoogle Scholar
  25. 25.
    Pantel K, Brakenhoff RH, Brandt B. Detection, clinical relevance and specific biological properties of disseminating tumor cells. Nat Rev Cancer. 2008;9:329–40.CrossRefGoogle Scholar
  26. 26.
    Went PT, Lugli A, Meier S, et al. Frequent EpCam protein expression in human carcinomas. Hum Pathol. 2004;35:122–8.CrossRefPubMedGoogle Scholar
  27. 27.
    Krebs MG, Sloane R, Priest L, et al. Evaluation and prognostic significance of circulating tumor cells in patients with non-small-cell lung cancer. J Clin Oncol. 2011;29:1556–63.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Yong-Jie Du
    • 1
  • Jian Li
    • 1
  • Wen-Fang Zhu
    • 1
  • Yan Wu
    • 2
  • Xin-Ping Tang
    • 1
  • Yi Wang
    • 3
  • Yi-Ming Hu
    • 1
  1. 1.Department of Pulmonary MedicineAffiliated Hospital of Jiangsu UniversityZhenjiangChina
  2. 2.Institute of Medical ScienceJiangsu UniversityZhenjiangChina
  3. 3.Center of Experimental MedicineAffiliated Hospital of Jiangsu UniversityZhenjiangChina

Personalised recommendations