Skip to main content

Advertisement

SpringerLink
Log in

Effects of vascular endothelial growth factor expression on pathological characteristics and prognosis of osteosarcoma

  • Original Article
  • Published:
Clinical and Experimental Medicine Aims and scope Submit manuscript

Abstract

Vascular endothelial growth factor (VEGF) has been linked with tumor invasion and metastasis. However, the role of VEGF expression in osteosarcoma remains controversial. By searching the PubMed, Embase, and Google Scholar databases, we conducted a meta-analysis to evaluate the pathological and prognostic significance of VEGF in osteosarcoma. Studies were pooled, and the odds ratio (OR) and its corresponding 95 % confidence interval (CI) were calculated. Nine relevant articles were included in this meta-analysis study. We performed pooled analysis with available data on the association between VEGF expression and age, gender, tumor stages IIB–III versus I–IIA, tumor recurrence, response to chemotherapy, and tumor metastasis. Our results revealed that VEGF expression might be closely associated with metastasis of osteosarcoma (OR 4.74, 95 % CI 2.53–8.87, P < 0.001). Furthermore, our findings also demonstrated that patients with grade IIB–III osteosarcoma showed a higher frequency of VEGF expression than those with grade I–IIA osteosarcoma (OR 5.33, 95 % CI 2.03–13.98, P = 0.001). We failed to find the association between VEGF expression and age (OR 0.82, 95 % CI 0.44–1.53, P = 0.539), gender (OR 1.33, 95 % CI 0.52–3.42, P = 0.553), tumor recurrence (OR 1.47, 95 % CI 0.56–3.86, P = 0.429), and response to chemotherapy (OR 1.26, 95 % CI 0.14–11.72, P = 0.839). In conclusion, VEGF is related to the grade and metastasis of osteosarcoma. It may play a significant role in clinical guidelines for the treatment and prognostic evaluation.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

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

Similar content being viewed by others

References

  1. Aung L, Tin AS, Quah TC, Pho RW. Osteogenic sarcoma in children and young adults. Ann Acad Med Singapore. 2014;43:305–13.

    PubMed  Google Scholar 

  2. Meyers PA, Gorlick R. Osteosarcoma. Pediatr Clin N Am. 1997;44:973–89.

    CAS  Google Scholar 

  3. Bacci G, Longhi A, Versari M, Mercuri M, Briccoli A, Picci P. Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15-year experience in 789 patients treated at a single institution. Cancer. 2006;106:1154–61.

    PubMed  Google Scholar 

  4. Link MP, Goorin AM, Miser AW, et al. The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med. 1986;314:1600–6.

    CAS  PubMed  Google Scholar 

  5. Coomber BL, Denton J, Sylvestre A, Kruth S. Blood vessel density in canine osteosarcoma. Can J Vet Res. 1998;62:199–204.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Ribatti D, Vacca A, Dammacco F. The role of the vascular phase in solid tumor growth: a historical review. Neoplasia. 1999;1:293–302.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Keck PJ, Hauser SD, Krivi G, Sanzo K, Warren T, Feder J, Connolly DT. Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science. 1989;246:1309–12.

    CAS  PubMed  Google Scholar 

  8. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 1989;246:1306–9.

    CAS  PubMed  Google Scholar 

  9. Ferrara N, Carver-Moore K, Chen H, et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature. 1996;380:439–42.

    CAS  PubMed  Google Scholar 

  10. Lee AH, Dublin EA, Bobrow LG, Poulsom R. Invasive lobular and invasive ductal carcinoma of the breast show distinct patterns of vascular endothelial growth factor expression and angiogenesis. J Pathol. 1998;185:394–401.

    CAS  PubMed  Google Scholar 

  11. Mattern J, Koomagi R, Volm M. Association of vascular endothelial growth factor expression with intratumoral microvessel density and tumor cell proliferation in human epidermoid lung carcinoma. Br J Cancer. 1996;73:931–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Berse B, Brown LF, Van De Water L, Dvorak HF, Senger DR. Vascular permeability factor (vascular endothelial growth factor) gene is expressed differentially in normal tissues, macrophages, and tumors. Mol Biol Cell. 1992;3:211–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Boocock CA, Charnock-Jones DS, Sharkey AM, et al. Expression of vascular endothelial growth factor and its receptors and KDR in ovarian carcinoma. J Natl Cancer Inst. 1995;87:506–16.

    CAS  PubMed  Google Scholar 

  14. Suzuki K, Hayashi N, Miyamoto Y, et al. Expression of vascular permeability factor/vascular endothelial growth factor in human hepatocellular carcinoma. Cancer Res. 1996;56:3004–9.

    CAS  PubMed  Google Scholar 

  15. Tokunaga T, Oshika Y, Abe Y, et al. Vascular endothelial growth factor (VEGF) mRNA isoform expression pattern correlated with liver metastasis and poor prognosis in colon cancer. Br J Cancer. 1998;77:998–1002.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Kaumaya PT, Foy KC. Peptide vaccines and targeting HER and VEGF proteins may offer a potentially new paradigm in cancer immunotherapy. Future Oncol. 2012;8:961–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Portal-Nuñez S, Lozano D, Esbrit P. Role of angiogenesis on bone formation. Histol Histopathol. 2012;27:559–66.

    PubMed  Google Scholar 

  18. 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;6:572–7.

    CAS  PubMed  Google Scholar 

  19. Jung ST, Moon ES, Seo HY, Kim JS, Kim GJ, Kim YK. Expression and significance of TGF-beta isoform and VEGF in osteosarcoma. Orthopedics. 2005;28:755–60.

    PubMed  Google Scholar 

  20. Huang Y, Lin Z, Zhuang J, Chen Y, Lin J. Prognostic significance of alpha V integrin and VEGF in osteosarcoma after chemotherapy. Onkologie. 2008;31(10):535–40.

    CAS  PubMed  Google Scholar 

  21. Mizobuchi H, García-Castellano JM, Philip S, Healey JH, Gorlick R. Hypoxia markers in human osteosarcoma: an exploratory study. Clin Orthop Relat Res. 2008;466(9):2052–9.

    PubMed  PubMed Central  Google Scholar 

  22. 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.

    CAS  PubMed  Google Scholar 

  23. Lin F, Zheng SE, Shen Z, et al. Relationships between levels of CXCR4 and VEGF and blood-borne metastasis and survival in patients with osteosarcoma. Med Oncol. 2011;28:649–53.

    CAS  PubMed  Google Scholar 

  24. Lammli J, Fan M, Rosenthal HG, et al. Expression of vascular endothelial growth factor correlates with the advance of clinical osteosarcoma. Int Orthop. 2012;36:2307–13.

    PubMed  PubMed Central  Google Scholar 

  25. Becker RG, Galia CR, Morini S, Viana CR. Immunohistochemical expression of vegf and her-2 proteins in osteosarcoma biopsies. Acta Orthop Bras. 2013;21(4):233–8.

    Google Scholar 

  26. Baptista AM, Camargo AF, Filippi RZ, Oliveira CR, Azevedo Neto RS, Camargo OP. Correlation between the expression of VEGF and survival in osteosarcoma. Acta Orthop Bras. 2014;22(5):250-5.

  27. Jawad MU, Scully SP. In brief: classifications in brief: enneking classification: benign and malignant tumors of the musculoskeletal system. Clin Orthop Relat Res. 2010;468:2000–2.

    PubMed  PubMed Central  Google Scholar 

  28. Folkman J. Seminars in medicine of the Beth Israel Hospital, Boston: clinical applications of research on angiogenesis. N Engl J Med. 1995;333:1757–63.

    CAS  PubMed  Google Scholar 

  29. Toi M, Matsumoto T, Bando H. Vascular endothelial growth factor: its prognostic, predictive, and therapeutic implications. Lancet Oncol. 2001;2:667–73.

    CAS  PubMed  Google Scholar 

  30. 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;17:291–5.

    CAS  PubMed  Google Scholar 

  31. Kaya M, Wada T, Kawaguchi S, et al. Increased pre-therapeutic serum vascular endothelial growth factor in patients with early clinical relapse of osteosarcoma. Br J Cancer. 2002;86:864–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Oshika Y, Nakamura M, Tokunaga T. Expression of cell-associated isoform of vascular endothelial growth factor 189 and its prognostic relevance in non-small cell lung cancer. Int J Oncol. 1998;12:541–4.

    CAS  PubMed  Google Scholar 

  33. Yin D, Jia T, Gong W, et al. VEGF blockade decelerates the growth of a murine experimental osteosarcoma. Int J Oncol. 2008;33:253–9.

    PubMed  Google Scholar 

  34. Zhuang Y, Wei M. Impact of vascular endothelial growth factor expression on overall survival in patients with osteosarcoma: a meta-analysis. Tumour Biol. 2014;35:1745–9.

    CAS  PubMed  Google Scholar 

  35. Yu XW, Wu TY, Yi X, et al. Prognostic significance of VEGF expression in osteosarcoma: a meta-analysis. Tumour Biol. 2014;35:155–60.

    CAS  PubMed  Google Scholar 

  36. Qu JT, Wang M, He HL, Tang Y, Ye XJ. The prognostic value of elevated vascular endothelial growth factor in patients with osteosarcoma: a meta-analysis and systemic review. J Cancer Res Clin Oncol. 2012;138:819–25.

    CAS  PubMed  Google Scholar 

  37. Rossi B, Schinzari G, Maccauro G, et al. Neoadjuvant multidrug chemotherapy including high-dose methotrexate modifies VEGF expression in osteosarcoma: an immunohistochemical analysis. BMC Musculoskelet Disord. 2010;11:34.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopaedics, General Hospital of Chinese PLA, No. 28, Fuxing Road, Haidian District, Beijing, 100853, China

    Gang Han, Yan Wang, Wenzhi Bi, Jinpeng Jia, Wei Wang & Meng Xu

Authors
  1. Gang Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wenzhi Bi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jinpeng Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Meng Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yan Wang.

Ethics declarations

Conflict of interest

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Han, G., Wang, Y., Bi, W. et al. Effects of vascular endothelial growth factor expression on pathological characteristics and prognosis of osteosarcoma. Clin Exp Med 16, 577–584 (2016). https://doi.org/10.1007/s10238-015-0382-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10238-015-0382-1

Keywords

Search

Navigation