Skip to main content

Advertisement

Log in

Prognostic value of survivin expression in breast cancer patients: a meta-analysis

  • Review
  • Published:
Tumor Biology

Abstract

The prognostic role of survivin expression in breast cancer patients has been widely reported. However, controversy still remains. Thus, a meta-analysis was conducted to obtain a more precise estimation of the relationship between survivin expression and overall survival (OS) in breast cancer patients. Relevant articles were selected for further assessment by online search in PubMed, EMBASE, and China National Knowledge Infrastructure. Pooled hazard ratios (HR) with 95 % confidence interval (95 % CI) were used to estimate the strength of the association between survivin expression and OS in breast cancer patients. Funnel plots of Begger’s and Egger’s linear regression test were used to evaluate the publication bias. Heterogeneity and sensitivity analysis were also assessed. Fifteen studies were included in the final analysis with the total number of 2,202 patients. There was a significant association between positive survivin expression and a poor OS consequence in patients with breast cancer (pooled HR 1.80, 95 % CI 1.55–2.09). No significant heterogeneity was observed among all the eligible studies (x 2 = 21.87, p = 0.081, I 2 = 36.0 %). Publication bias was absent. Sensitivity analysis revealed that the results of this meta-analysis were robust. Our results suggested that high survivin expression had an unfavorable prognostic role for patients with breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  2. Huang ZZ, Chen WQ, Wu CX, Zheng RS, Chen JG, Yang NN, et al. Incidence and mortality of female breast cancer in China—a report from 32 Chinese cancer registries. Tumor. 2012;32:435–9.

    Google Scholar 

  3. Bennett RL, Blanks RG, Patnick J, Moss SM. Results from the UK NHS breast screening programme 2000–05. J Med Screen. 2007;14:200–4.

    Article  PubMed  CAS  Google Scholar 

  4. Ferguson NL, Bell J, Heidel R, Lee S, Vanmeter S, Duncan L, et al. Prognostic value of breast cancer subtypes, ki-67 proliferation index, age, and pathologic tumor characteristics on breast cancer survival in Caucasian women. Breast J. 2013;19:22–30.

    Article  PubMed  Google Scholar 

  5. Gebauer G, Fehm T, Lang N, Jager W. Tumor size, axillary lymph node status and steroid receptor expression in breast cancer: prognostic relevance 5 years after surgery. Breast Cancer Res Treat. 2002;75:167–73.

    Article  PubMed  CAS  Google Scholar 

  6. Duraker N, Caynak ZC. Prognostic value of the 2002 TNM classification for breast carcinoma with regard to the number of metastatic axillary lymph nodes. Cancer. 2005;104:700–7.

    Article  PubMed  Google Scholar 

  7. Coradini D, Daidone MG. Biomolecular prognostic factors in breast cancer. Curr Opin Obstet Gynecol. 2004;16:49–55.

    Article  PubMed  Google Scholar 

  8. Rodel F, Sprenger T, Kaina B, Liersch T, Rodel C, Fulda S, et al. Survivin as a prognostic/predictive marker and molecular target in cancer therapy. Curr Med Chem. 2012;19:3679–88.

    Article  PubMed  CAS  Google Scholar 

  9. Sah NK, Khan Z, Khan GJ, Bisen PS. Structural, functional and therapeutic biology of survivin. Cancer Lett. 2006;244:164–71.

    Article  PubMed  CAS  Google Scholar 

  10. Kanwar JR, Kamalapuram SK, Kanwar RK. Targeting survivin in cancer: patent review. Expert Opin Ther Pat. 2010;20:1723–37.

    Article  PubMed  CAS  Google Scholar 

  11. Stauber RH, Mann W, Knauer SK. Nuclear and cytoplasmic survivin: molecular mechanism, prognostic, and therapeutic potential. Cancer Res. 2007;67:5999–6002.

    Article  PubMed  CAS  Google Scholar 

  12. Tamm I, Wang Y, Sausville E, Scudiero DA, Vigna N, Oltersdorf T, et al. IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res. 1998;58:5315–20.

    PubMed  CAS  Google Scholar 

  13. Yamamoto T, Tanigawa N. The role of survivin as a new target of diagnosis and treatment in human cancer. Med Electron Microsc. 2001;34:207–12.

    Article  PubMed  CAS  Google Scholar 

  14. Suzuki A, Ito T, Kawano H, Hayashida M, Y H, Tsutomi Y, et al. Survivin initiates procaspase-3/p21 complex formation as a result of interaction with CDK4 to resist Fas-mediated cell death. Oncogene. 2000;19:1346–51.

    Article  PubMed  CAS  Google Scholar 

  15. Zhang LQ, Wang J, Jiang F, Xu L, Liu FY, Yin R. Prognostic value of survivin in patients with non-small cell lung carcinoma: a systematic review with meta-analysis. PLoS One. 2012;7:e34100.

    Article  PubMed  CAS  Google Scholar 

  16. Li C, Li Z, Zhu M, Zhao T, Chen L, Ji W, et al. Clinicopathological and prognostic significance of survivin over-expression in patients with esophageal squamous cell carcinoma: a meta-analysis. PLoS One. 2012;7:e44764.

    Article  PubMed  CAS  Google Scholar 

  17. Li Y, Tan BB, Fan LQ, Zhao Q, Liu Y, Wang D. Expression of COX-2, survivin in regional lymph node metastases of gastric carcinoma and the correlation with prognosis. Hepatogastroenterology. 2010;57:1435–41.

    PubMed  CAS  Google Scholar 

  18. Fristrup N, Ulhai BP, Birkenkamp-Demtrider K, Mansilla F, Sanchez-Carbayo M, Segersten U, et al. Cathepsin E, maspin, Plk1, and survivin are promising prognostic protein markers for progression in non-muscle invasive bladder cancer. Am J Pathol. 2012;180:1824–34.

    Article  PubMed  CAS  Google Scholar 

  19. Yakirevich E, Samkari A, Holloway MP, Lu S, Singh K, Yu J, et al. Total Survivin and acetylated Survivin correlate with distinct molecular subtypes of breast cancer. Hum Pathol. 2012;43:865–73.

    Article  PubMed  CAS  Google Scholar 

  20. Athanassiadou AM, Patsouris E, Tsipis A, Gonidi M, Athanassiadou P. The significance of Survivin and Nectin-4 expression in the prognosis of breast carcinoma. Folia Histochem Cytobiol. 2011;49:26–33.

    PubMed  CAS  Google Scholar 

  21. Rexhepaj E, Jirstrom K, O'Connor DP, O'Brien SL, Landberg G, Duffy MJ, et al. Validation of cytoplasmic-to-nuclear ratio of survivin as an indicator of improved prognosis in breast cancer. BMC Cancer. 2010;10:639.

    Article  PubMed  Google Scholar 

  22. Massidda B, Sini M, Budroni M, Atzori F, Deidda M, Pusceddu V, et al. Molecular alterations in key-regulator genes among patients with T4 breast carcinoma. BMC Cancer. 2010;10:458.

    Article  PubMed  Google Scholar 

  23. Nassar A, Lawson D, Cotsonis G, Cohen C. Survivin and caspase-3 expression in breast cancer: correlation with prognostic parameters, proliferation, angiogenesis, and outcome. Appl Immunohistochem Mol Morphol. 2008;16:113–20.

    Article  PubMed  CAS  Google Scholar 

  24. Tsai WC, Chu CH, Yu CP, Sheu LF, Chen A, Chiang H, et al. Matriptase and survivin expression associated with tumor progression and malignant potential in breast cancer of Chinese women: tissue microarray analysis of immunostaining scores with clinicopathological parameters. Dis Markers. 2008;24:89–99.

    Article  PubMed  CAS  Google Scholar 

  25. Brennan DJ, Rexhepaj E, O'Brien SL, McSherry E, O'Connor DP, Fagan A, et al. Altered cytoplasmic-to-nuclear ratio of survivin is a prognostic indicator in breast cancer. Clin Cancer Res. 2008;14:2681–9.

    Article  PubMed  CAS  Google Scholar 

  26. Guan HT, Xue FJ, Wang XJ, Xue XH, Liu XX, Dai ZJ, et al. Prognostic value of survivin expression in breast cancer. Modern Oncology. 2007;15:938–40.

    CAS  Google Scholar 

  27. Zheng CH, Wang C, Zhang XF, Lu HS, Huang CM. Expression and significance of survivin in breast cancer. Journal of Fujian Medical University. 2007;41:316–8.

    Google Scholar 

  28. Al-Joudi FS, Iskandar ZA, Imran AK. Survivin expression correlates with unfavourable prognoses in invasive ductal carcinoma of the breast. Med J Malaysia. 2007;62:6–8.

    PubMed  CAS  Google Scholar 

  29. Sohn DM, Kim SY, Baek MJ, Lim CW, Lee MH, Cho MS, et al. Expression of survivin and clinical correlation in patients with breast cancer. Biomed Pharmacother. 2006;60:289–92.

    Article  PubMed  CAS  Google Scholar 

  30. Zhang RX, Fan J, Wang SY, Wang L, Wang CF, Li TD. Expression and clinical significance of Survivin in breast cancer. Chin J Cancer Prev Treat. 2005;12:1476–9.

    CAS  Google Scholar 

  31. Mao J, Hai J, Shu HP, Tang LL, Shen ZT, Wu YH, et al. Relationship of oncogene survivin, p53 expression in breast cancer and its prognostic significance. Chinese Journal of General Surgery. 2005;14:265–8.

    CAS  Google Scholar 

  32. Kennedy SM, O'Driscoll L, Purcell R, Fitz-Simons N, McDermott EW, Hill AD, et al. Prognostic importance of survivin in breast cancer. Br J Cancer. 2003;88:1077–83.

    Article  PubMed  CAS  Google Scholar 

  33. Tanaka K, Iwamoto S, Gon G, Nohara T, Iwamoto M, Tanigawa N. Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. Clin Cancer Res. 2000;6:127–34.

    PubMed  CAS  Google Scholar 

  34. Youssef NS, Hewedi IH, Abd Raboh NM. Immunohistochemical expression of survivin in breast carcinoma: relationship with clinicopathological parameters, proliferation and molecular classification. J Egypt Natl Canc Inst. 2008;20:348–57.

    PubMed  Google Scholar 

  35. Singh M, Bleile MJ, Shroyer AL, Heinz D, Jarboe EA, Shroyer KR. Analysis of survivin expression in a spectrum of benign to malignant lesions of the breast. Appl Immunohistochem Mol Morphol. 2004;12:296–304.

    Article  PubMed  CAS  Google Scholar 

  36. Sang ZF, Wang X, Qi YX, Zhao GQ. Expression of survivin in breast carcinoma and its relationship with K-i 67 and c-erbB-2. Cancer Research on Prevention and Treatment. 2010;37:773–6.

    Google Scholar 

  37. Nordmann AJ, Kasenda B, Briel M. Meta-analyses: what they can and cannot do. Swiss Med Wkly. 2012;142:w13518.

    PubMed  Google Scholar 

  38. Qian Q, Wang Q, Zhan P, Peng L, Wei SZ, Shi Y, et al. The role of matrix metalloproteinase 2 on the survival of patients with non-small cell lung cancer: a systematic review with meta-analysis. Cancer Invest. 2010;28:661–9.

    Article  PubMed  Google Scholar 

  39. Peng WJ, Zhang JQ, Wang BX, Pan HF, Lu MM, Wang J. Prognostic value of matrix metalloproteinase 9 expression in patients with non-small cell lung cancer. Clin Chim Acta. 2012;413:1121–6.

    Article  PubMed  CAS  Google Scholar 

  40. Gould Rothberg BE, Bracken MB. E-cadherin immunohistochemical expression as a prognostic factor in infiltrating ductal carcinoma of the breast: a systematic review and meta-analysis. Breast Cancer Res Treat. 2006;100:139–48.

    Article  PubMed  CAS  Google Scholar 

  41. Tong J, Sun X, Cheng H, Zhao D, Ma J, Zhen Q, et al. Expression of p16 in non- small cell lung cancer and its prognostic significance: a meta-analysis of published literatures. Lung Cancer. 2011;74:155–63.

    Article  PubMed  Google Scholar 

  42. McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM, et al. Reporting recommendations for tumor marker prognostic studies (remark). Exp Oncol. 2006;28:99–105.

    PubMed  CAS  Google Scholar 

  43. Chen M, Cai E, Huang J, Yu P, Li K. Prognostic value of vascular endothelial growth factor expression in patients with esophageal cancer: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2012;21:1126–34.

    Article  PubMed  CAS  Google Scholar 

  44. Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;7:8–16.

    Google Scholar 

  45. Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998;17:2815–34.

    Article  PubMed  CAS  Google Scholar 

  46. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.

    Article  PubMed  CAS  Google Scholar 

  47. Petrarca CR, Brunetto AT, Duval V, Brondani A, Carvalho GP, Garicochea B. Survivin as a predictive biomarker of complete pathologic response to neoadjuvant chemotherapy in patients with stage II and stage III breast cancer. Clin Breast Cancer. 2011;11:129–34.

    Article  PubMed  CAS  Google Scholar 

  48. Nassar A, Sexton D, Cotsonis G, Cohen C. Survivin expression in breast carcinoma: correlation with apoptosis and prognosis. Appl Immunohistochem Mol Morphol. 2008;16:221–6.

    Article  PubMed  CAS  Google Scholar 

  49. Son BH, Choi JS, Lee JH. Prognostic values of KAI1 and survivin expression in an infiltrating ductal carcinoma of the breast. Pathology. 2005;37:131–6.

    Article  PubMed  CAS  Google Scholar 

  50. Lu W, Zhang Y, Tong HX. Prediction of breast cancer prognosis by midkine, survivin and mmp2 detection. Chinese Journal of Clinical Medicine. 2009;16:964–6.

    Google Scholar 

  51. Chen XJ, Cai QF. Expressions of survivin and PCNA in breast carcinoma and their clinical significance. Journal of Hainan Medical University. 2005;11:259–61.

    Google Scholar 

  52. Dogu GG, Ozkan M, Ozturk F, Dikilitas M, Er O, Ozturk A. Triple-negative breast cancer: immunohistochemical correlation with basaloid markers and prognostic value of survivin. Med Oncol. 2010;27:34–9.

    Article  PubMed  CAS  Google Scholar 

  53. Kleinberg L, Flarenes VA, Nesland JM, Davidson B. Survivin, a member of the inhibitors of apoptosis family, is down-regulated in breast carcinoma effusions. Am J Clin Pathol. 2007;128:389–97.

    Article  PubMed  CAS  Google Scholar 

  54. Barnes N, Haywood P, Flint P, Knox WF, Bundred NJ. Survivin expression in in situ and invasive breast cancer relates to COX-2 expression and DCIS recurrence. Br J Cancer. 2006;94:253–8.

    Article  PubMed  CAS  Google Scholar 

  55. Span PN, Tjan-Heijnen VC, Manders P, Van TD, Lehr J, Sweep FC. High survivin predicts a poor response to endocrine therapy, but a good response to chemotherapy in advanced breast cancer. Breast Cancer Res Treat. 2006;98:223–30.

    Article  PubMed  CAS  Google Scholar 

  56. Span PN, Tjan-Heijnen VC, Heuvel JJ, de Kok JB, Foekens JA, Sweep FC. Do the survivin (BIRC5) splice variants modulate or add to the prognostic value of total survivin in breast cancer? Clin Chem. 2006;52:1693–700.

    Article  PubMed  CAS  Google Scholar 

  57. Ghayad SE, Vendrell JA, Bieche I. Identification of TACC1, NOV, and PTTG1 as new candidate genes associated with endocrine therapy resistance in breast cancer. J Mol Endocrinol. 2009;42:87–103.

    Article  PubMed  CAS  Google Scholar 

  58. Yamashita S, Masuda Y, Kurizaki T, Haga Y, Murayama T, Ikei S, et al. Survivin expression predicts early recurrence in early-stage breast cancer. Anticancer Res. 2007;27:2803–8.

    PubMed  CAS  Google Scholar 

  59. Boidot R, Vegran F, Lizard-Nacol S. Predictive value of survivin alternative transcript expression in locally advanced breast cancer patients treated with neoadjuvant chemotherapy. Int J Mol Med. 2009;23:285–91.

    PubMed  CAS  Google Scholar 

  60. Span PN, Sweep FC, Wiegerinck ET, Tjan-Heijnen VC, Manders P, Beex LV, et al. Survivin is an independent prognostic marker for risk stratification of breast cancer patients. Clin Chem. 2004;50:1986–93.

    Article  PubMed  CAS  Google Scholar 

  61. Ryan BM, Konecny GE, Kahlert S, Wang HJ, Untch M, Meng G, et al. Survivin expression in breast cancer predicts clinical outcome and is associated with HER2, VEGF, urokinase plasminogen activator and PAI-1. Ann Oncol. 2006;17:597–604.

    Article  PubMed  CAS  Google Scholar 

  62. Ionta MT, Perra MT, Atzori F, Maxia C, Pusceddu V, Demurtas P, et al. Long-term maintenance of prognostic value of survivin and its relationship with p53 in T4 breast cancer patients. Exp Ther Med. 2010;1:59–64.

    PubMed  Google Scholar 

  63. Koziol JA, Zhang JY, Casiano CA, Peng XX, Shi FD, Feng AC, et al. Recursive partitioning as an approach to selection of immune markers for tumor diagnosis. Clin Cancer Res. 2003;9:120e6.

    Google Scholar 

  64. Singh M, Bleile MJ, Shroyer AL, Heinz D, Jarboe EA, Shroyer KR. Analysis of survivin expression in a spectrum of benign to malignant lesions of the breast. Appl Immunohistochem Mol Morphol. 2004;12:296e304.

    Article  Google Scholar 

  65. Li X, Dang X, Sun X. Expression of survivin and VEGF-C in breast cancer tissue and its relation to lymphatic metastasis. Eur J Gynaecol Oncol. 2012;33:178–82.

    PubMed  CAS  Google Scholar 

  66. Guo H, Wei B, Zhang HY, Liu GJ, Bu H, Lang ZQ, et al. HER2 expression and its prognostic implication in lymph node negative breast carcinoma: a meta-analysis. Zhonghua Bing Li Xue Za Zhi. 2005;34:140–6.

    Google Scholar 

  67. Wang J, Guo Y, Wang B, Bi J, Li K, Liang X, et al. Lymphatic microvessel density and vascular endothelial growth factor-C and -D as prognostic factors in breast cancer: a systematic review and meta-analysis of the literature. Mol Biol Rep. 2012;39:11153–65.

    Article  PubMed  CAS  Google Scholar 

  68. Jha K, Shukla M, Pandey M. Survivin expression and targeting in breast cancer. Surg Oncol. 2012;21:125–31.

    Article  PubMed  Google Scholar 

  69. Carrasco RA, Stamm NB, Marcusson E, Sandusky G, Iversen P, Patel BK. Antisense inhibition of survivin expression as a cancer therapeutic. Mol Cancer Ther. 2011;10:221–32.

    Article  PubMed  CAS  Google Scholar 

  70. Eroles P, Bosch A, Pérez-Fidalgo JA, Lluch A. Molecular biology in breast cancer: intrinsic subtypes and signaling pathways. Cancer Treat Rev. 2012;38:698–707.

    Article  PubMed  CAS  Google Scholar 

  71. Podo F, Buydens LM, Degani H, Hilhorst R, Klipp E, Gribbestad IS, et al. Triple-negative breast cancer: present challenges and new perspectives. Mol Oncol. 2010;4:209–29.

    Article  PubMed  CAS  Google Scholar 

Download references

Conflicts of interest

None

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hong Su.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Song, J., Su, H., Zhou, Yy. et al. Prognostic value of survivin expression in breast cancer patients: a meta-analysis. Tumor Biol. 34, 2053–2062 (2013). https://doi.org/10.1007/s13277-013-0848-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-013-0848-2

Keywords

Navigation