Skip to main content

Advertisement

Log in

Prognostic significance of VEGF expression in osteosarcoma: a meta-analysis

  • Research Article
  • Published:
Tumor Biology

Abstract

Vascular endothelial growth factor (VEGF) is considered as a prime mediator of angiogenesis and has been implicated in carcinogenesis and metastasis. Various studies examined the relationship between VEGF overexpression with the clinical outcome in patients with osteosarcoma but yielded conflicting results. Electronic databases updated to April 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between VEGF overexpression and survival of patients with osteosarcoma. Survival data were aggregated and quantitatively analyzed. We performed a meta-analysis of eight studies that evaluated the correlation between VEGF overexpression and survival in patients with osteosarcoma. Combined hazard ratios suggested that VEGF overexpression had an unfavorable impact on overall survival (hazard ratio (HR) = 1.75, 95 % confidence interval (CI): 1.21–2.28) in patients with osteosarcoma for overall populations, 2.37 (1.35–3.39) in Asian studies but not in non-Asian studies (HR = 1.51, 95 % CI: 0.89–2.14). No significant heterogeneity was observed among all studies. VEGF overexpression indicates a poor prognosis for patients with osteosarcoma. However, the prognostic value of VEGF on survival in osteosarcoma patients still needs further large-scale prospective trials to be clarified.

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

Similar content being viewed by others

References

  1. Mirra JM, Gold RH, Picci P. Osseous tumors of intramedullary origin. In: Mirra JM, editor. Bone tumors: clinical radiologic, and pathologic correlations. Philadelphia: Lea and Febiger; 1989. p. 143–438.

    Google Scholar 

  2. Bielack S, Jürgens H, Jundt G, et al. Osteosarcoma: the COSS experience. Cancer Treat Res. 2010;152:289–308.

    Article  Google Scholar 

  3. Davis AM, Bell RS, Goodwin PJ. Prognostic factors in osteo-sarcoma: a critical review. J Clin Oncol. 1994;12:423–31.

    CAS  PubMed  Google Scholar 

  4. Bacci G, Longhi A, Versari M, et al. Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemo-therapy: 15-year experience in 789 patients treated at a single institution. Cancer. 2006;1:1154–61.

    Article  Google Scholar 

  5. Ferrara N. VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer. 2002;2:795–803.

    Article  CAS  PubMed  Google Scholar 

  6. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005;23:1011–27.

    Article  CAS  PubMed  Google Scholar 

  7. Altman DG. Systematic reviews of evaluations of prognostic variables. BMJ. 2001;323(7306):224–8.

    Article  CAS  PubMed  Google Scholar 

  8. Zhan P, Qian Q, Yu LK. Prognostic value of COX-2 expression in patients with non-small cell lung cancer: a systematic review and meta-analysis. J Thorac Dis. 2013;5(1):40–7. doi:10.3978/j.issn.2072-1439.2013.01.02.

    PubMed Central  PubMed  Google Scholar 

  9. Zhan P, Qian Q, Wan B, Yan TD, Yu LK. Prognostic value of TTF-1 expression in patients with non-small cell lung cancer: a meta-analysis. Transl Cancer Res. 2013;2(1):25–32. doi:10.3978/j.issn.2218-676X.2013.02.08.

    Google Scholar 

  10. Zhan P, Wang Q, Qian Q, Yu LK. Megestrol acetate in cancer patients with anorexia-cachexia syndrome: a meta-analysis. Transl Cancer Res. 2013;2(2):74–9. doi:10.3978/j.issn.2218-676X.2013.04.13.

    Google Scholar 

  11. Zhan P, Wang Q, Qian Q, Yu LK. Risk of venous thromboembolism with the erythropoiesis-stimulating agents (ESAs) for the treatment of cancer-associated anemia: a meta-analysis of randomized control trials. Clin Oncol: Chin; 2013 Jan 03.

  12. Zhan P, Qian Q, Yu LK. Prognostic significance of vascular endothelial growth factor expression in hepatocellular carcinoma tissue: a meta-analysis. Hepatobiliary Surg Nutr 2013 Jun 21. doi: 10.3978/j.issn.2304-3881.2013.06.06

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

    Article  CAS  PubMed  Google Scholar 

  14. Yusuf S, Peto R, Lewis J, et al. Blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis. 1985;27:335–71.

    Article  CAS  PubMed  Google Scholar 

  15. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.

    Article  CAS  PubMed  Google Scholar 

  16. Egger M, Smith GD, Schneider M. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.

    Article  CAS  PubMed  Google Scholar 

  17. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.

    Article  CAS  PubMed  Google Scholar 

  18. Lee YH, Tokunaga T, Oshika Y, et al. Cell-retained isoforms of vascular endothelial growth factor (VEGF) are correlated with poor prognosis in osteosarcoma. Eur J Cancer. 1999;35(7):1089–93.

    Article  CAS  PubMed  Google Scholar 

  19. Handa A, Tokunaga T, Tsuchida T, et al. Neuropilin-2 expression affects the increased vascularization and is a prognostic factor in osteosarcoma. Int J Oncol. 2000;17(2):291–5.

    CAS  PubMed  Google Scholar 

  20. Kaya M, Wada T, Akatsuka T, et al. Vascular endothelial growth factor expression in untreated osteosarcoma is predictive of pulmonary metastasis and poor prognosis. Clin Cancer Res. 2000;6(2):572–7.

    CAS  PubMed  Google Scholar 

  21. Jung ST, Moon ES, Seo HY, Kim JS, Kim GJ, Kim YK. Expression and significance of TGF-beta isoform and VEGF in osteosar-coma. Orthopedics. 2005;28(8):755–60.

    PubMed  Google Scholar 

  22. Charity RM, Foukas AF, Deshmukh NS, Grimer RJ. Vascular endothelial growth factor expression in osteosarcoma. Clin Orthop Relat Res. 2006;448:193–8.

    Article  CAS  PubMed  Google Scholar 

  23. Ek ET, Ojaimi J, Kitagawa Y, Choong PF. Does the degree of intratumoural microvessel density and VEGF expression have prognostic significance in osteosarcoma. Oncol Rep. 2006;16(1):17–23.

    CAS  PubMed  Google Scholar 

  24. Oda Y, Yamamoto H, Tamiya S, et al. CXCR4 and VEGF expression in the primary site and the metastatic site of human osteosarcoma: analysis within a group of patients, all of whom developed lung metastasis. Mod Pathol. 2006;19(5):738–45.

    Article  CAS  PubMed  Google Scholar 

  25. Abdeen A, Chou AJ, Healey JH, et al. Correlation between clinical outcome and growth factor pathway expression in osteogenic sarcoma. Cancer. 2009;115(22):5243–50.

    Article  PubMed  Google Scholar 

  26. Kaya M, Wada T, Nagoya S, Sasaki M, Matsumura T, Yamashita T. The level of vascular endothelial growth factor as a predictor of a poor prognosis in osteosarcoma. J Bone Joint Surg Br. 2009;91(6):784–8.

    Article  CAS  PubMed  Google Scholar 

  27. Boulytcheva IV, Soloviev YN, Kushlinskii NE, Mahson AN. Expression of molecular markers in the tumor and survival prognosis in osteosarcoma. Bull Exp Biol Med. 2010;150(2):237–42.

    Article  CAS  PubMed  Google Scholar 

  28. Zhou Q, Zhu Y, Deng Z, Long H, Zhang S, Chen X. VEGF and EMMPRIN expression correlates with survival of patients with osteosarcoma. Surg Oncol. 2011;20(1):13–9.

    Article  CAS  PubMed  Google Scholar 

  29. Ługowska I, Woźniak W, Klepacka T, Michalak E, Szamotulska K. A prognostic evaluation of vascular endothelial growth factor in children and young adults with osteosarcoma. Pediatr Blood Cancer. 2011;15;57(1):63–8.

    Article  Google Scholar 

  30. Chen Y, Wang CM, Shi YQ, Yang Y. Expression of hypoxia-inducible factor 1α in osteosarcoma and its value in predicting chemosensitivity [in Chinese]. Chien J Oncol. 2012;34(12):899–904.

    CAS  Google Scholar 

  31. Parikh AA, Ellis LM. The vascular endothelial growth factor family and its receptors. Hematol Oncol Clin North Am. 2004;18(5):951–71. vii.

    Article  PubMed  Google Scholar 

  32. Xie K, Wei D, Shi Q, Huang S. Constitutive and inducible expression and regulation of vascular endothelial growth factor. Cytokine Growth Factor Rev. 2004;15(5):297–324.

    Article  CAS  PubMed  Google Scholar 

  33. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005;23(5):1011–27.

    Article  CAS  PubMed  Google Scholar 

  34. Kyzas PA, Cunha IW, Ioannidis JP. Prognostic significance of vascular endothelial growth factor immunohistochemical expression in head and neck squamous cell carcinoma: a meta-analysis. Clin Cancer Res. 2005;11(4):1434–40.

    Article  CAS  PubMed  Google Scholar 

  35. Zhan P, Wang J, Lv XJ, Wang Q, Qiu LX, Lin XQ, et al. Prognostic value of vascular endothelial growth factor expression in patients with lung cancer: a systematic review with meta-analysis. J Thorac Oncol. 2009;4(9):1094–103.

    Article  PubMed  Google Scholar 

  36. Des Guetz G, Uzzan B, Nicolas P, Cucherat M, Morere JF, Benamouzig R, et al. Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature Br J Cancer. 2006;94(12):1823–32.

    CAS  Google Scholar 

  37. Peng L, Zhan P, Zhou Y, Fang W, Zhao P, Zheng Y, et al. Prognostic significance of vascular endothelial growth factor immunohistochemical expression in gastric cancer: a meta-analysis. Mol Biol Rep. 2012 Oct;39(10):9473–84.

  38. Schoenleber SJ, Kurtz DM, Talwalkar JA, Roberts LR, Gores GJ. Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and meta-analysis. Br J Cancer. 2009;100(9):1385–92.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Kowanetz M, Ferrara N. Vascular endothelial growth factor signaling pathways: therapeutic perspective. Clin Cancer Res. 2006;12(17):5018–22.

    Article  CAS  PubMed  Google Scholar 

  40. Ranieri G, Patruno R, Ruggieri E, Montemurro S, Valerio P, Ribatti D. Vascular endothelial growth factor (VEGF) as a target of bevacizumab in cancer: from the biology to the clinic. Curr Med Chem. 2006;13(16):1845–57.

    Article  CAS  PubMed  Google Scholar 

  41. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355(24):2542–50.

    Article  CAS  PubMed  Google Scholar 

  42. Xu T, Chen J, Lu Y, Wolff JE. Effects of bevacizumab plus irinotecan on response and survival in patients with recurrent malignant glioma: a systematic review and survival-gain analysis. BMC Cancer. 2010;10:252.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Begg CB, Berlin JA. Publication bias: a problem in interpreting medical data. J R Stat Soc A. 1988;151:419–63.

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (no. 81071487), the Social Development Program of Jiangsu Province (no. BE2010744), Medical Scientific Research Foundation of Jiangsu Province (no. H201008), the Program for Medical Talents of Jiangsu Province (no. H201122), China Postdoctoral Science Foundation (no. 20100480598), and the Shanghai Postdoctoral Sustentation Fund (no. 11R21414400), the Natural Science Foundation of Shanghai Municipal Health Bureau (no. 20114y079); the Medicine and Engineering Foundation of Shanghai Jiaotong University (no. YG2011MS33).

Conflicts of interest

None

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chang-qing Zhang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yu, XW., Wu, TY., Yi, X. et al. Prognostic significance of VEGF expression in osteosarcoma: a meta-analysis. Tumor Biol. 35, 155–160 (2014). https://doi.org/10.1007/s13277-013-1019-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-013-1019-1

Keywords

Navigation