Skip to main content

Advertisement

Log in

Role of Serum Vascular Endothelial Growth Factor in the Prediction of Angiogenesis and Prognosis for Non-small Cell Lung Cancer

  • Published:
Lung Aims and scope Submit manuscript

Abstract

Although vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 are involved in angiogenesis of various cancers, clinical utility of preoperative serum concentration of these molecules in non-small cell lung cancer (NSCLC) has not yet been elucidated. In this study, we determined the concentration of VEGF, MMP-9 and various other tumor markers in serum prior to surgery and evaluated the results compared with intratumoral vasculature to isolate a valuable marker in determining the prediction of angiogenesis in NSCLC. Among these molecules and serum tumor markers, circulating serum VEGF was identified to markedly correlate with microvessel density (MVD) of the resected tumor specimens. Moreover, overall survival of patients with low VEGF levels (≤326 ng/ml) was significantly greater than that of patients with high VEGF levels (>326 ng/ml), while patients with low MMP-9 levels (≤189 ng/ml) and those with high MMP-9 levels (>189 ng/ml) revealed similar overall survival. Conclusively, preoperative concentration of serum VEGF may be the most valuable marker in the prediction of intratumoral angiogenesis and prognosis of patients with NSCLC.

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. J Adams P Carder S Downey et al. (2000) ArticleTitlevascular endothelial growth factor (VEGF) in breast cancer: comparison of plasma, serum, and tissue VEGF and microvessel density and effects of tamxifen Cancer Res 60 2898–2905

    Google Scholar 

  2. H Aikawa H Takahashi S Fujimura et al. (1999) ArticleTitleImmunohistochemical study of tumor angiogenic facotrs in non-small cell lung cancer Anticancer Res 19 4305–4309

    Google Scholar 

  3. A Balsari J Maier I Maria S Menard (1999) ArticleTitleCorrelation between growth factor production by tumor cells, serum vascular endothelial growth factor levels, and serum angiogenic activity in patients with breast carcinoma Lab Invest 79 897–902

    Google Scholar 

  4. R Bicknell A Harris (1991) ArticleTitleNovel growth regulatory factors and tumor angiogenesis Eur J Cancer 1991 781–784

    Google Scholar 

  5. G Byrne N Bundred (2000) ArticleTitleSurrogate markers of tumoral angiogenesis Int J Biol Markers 15 334–339

    Google Scholar 

  6. G Callagy E Dimitriadis J Harmey D Bouchier-Hayes M Leader E Kay (2000) ArticleTitleImmunohistochemical measurement of tumor vascular endothelial growth factor in breast cancer. A more reliable predictor of tumor stage than microvessel density or serum vascular endothelial growth factor Appl Immunohistochem Mol Morphol 8 104–109

    Google Scholar 

  7. J Choi H Kirn H Lim et al. (2001) ArticleTitleVascular endothelial growth factor in the serum of patients with non-small cell lung cancer: correlation with platelet and leukocyte counts Lung Cancer 33 171–179

    Google Scholar 

  8. G Cox JL Jones A Andi DA Waller KJ O’Byrne (2001) ArticleTitleA biological staging model for operable non-small cell lung cancer Thorax 56 561–566

    Google Scholar 

  9. M Davies S Jonas S Kaur T Allen-Mersh (2000) ArticleTitlePlasma vascular endothelial but not fibroblast growth factor levels correlate with colorectal liver metastasis vascularity and volume Br J Cancer 82 1004–1008

    Google Scholar 

  10. D Dhar T Ono A Yamanoi et al. (2002) ArticleTitleSerum endostatin predicts tumor vascularity in hepatocellular carcinoma Cancer 95 2188–2195

    Google Scholar 

  11. J Folkman K Watson D Ingber D Hanahan (1989) ArticleTitleInduction of angiogenesis during the transition from hyperplasia to neoplasia Nature 339 58–61

    Google Scholar 

  12. G Fontanini S Vignati L Boldrini et al. (1997) ArticleTitleVascular endothelial growth factor is associated with neovascularization and influences progression of non-small cell lung carcinoma Clin Cancer Res 3 861–865

    Google Scholar 

  13. A Giatromanolaki (2000) ArticleTitleDifferential expression of angiogenic and of vascular survival factors in non-small cell lung cancer (NSCLC) Adv Exp Med Biol 476 291–295

    Google Scholar 

  14. DJ Harpole W Richard JN Herndon D Sugarbaker (1996) ArticleTitleAngiogenesis and molecular biologic substaging in patients with stage I non-small cell lung cancer Ann Thorac Surg 61 1470–1476

    Google Scholar 

  15. L Hefler C Tempfer A Obermair et al. (1999) ArticleTitleSerum concentrations of vascular endothelial growth factor in vulvar cancer Clin Cancer Res 5 2806–2809

    Google Scholar 

  16. H Imoto T Osaki S Taga A Ohgami Y Ichiyoshi K Yasumoto (1998) ArticleTitleVascular endothelial growth factor expression in non-small-cell lung cancer: prognostic significance in squamous cell carcinoma J Thorac Cardiovasc Surg 115 1007–1014

    Google Scholar 

  17. B Johnson (2003) ArticleTitleAdjuvant chemotherapy for non-small cell lung cancer: the end of the beginning J Natl Cancer Inst 95 1422–1424

    Google Scholar 

  18. S Kaneko K Ishikawa I Yoshimi et al. (2003) ArticleTitleProjection of lung cancer mortality in Japan Cancer Sci 94 919–923

    Google Scholar 

  19. E Laack A Kohler C Kugler et al. (2002) ArticleTitlePretreatment serum levels of matrix metalloproteinase-9 and vascular endothelial growth factor in non-small-cell lung cancer Ann Oncol 13 1550–1557

    Google Scholar 

  20. T Lantzsch L Hefler U Krause et al. (2002) ArticleTitleThe correlation between immunohistochemically-detected markers of angiogenesis and serum vascular endothelial growth factor in patients with breast cancer Anticancer Res 22 1925–1928

    Google Scholar 

  21. T Marugome S Mizuno (2003) ArticleTitleMortality trend of lung cancer in Japan: 1960–2000 Jpn J Clin Oncol 33 148–149

    Google Scholar 

  22. J Mattern R Koomagi M Volm (1999) ArticleTitleBiological characterization of subgroups of squamous cell lung carcinomas Clin Cancer Res 5 1459–1463

    Google Scholar 

  23. J Mattern R Koomaqi M Volm (1996) ArticleTitleAssociation of vascular endothelial growth factor expression with intratumoral microvessel density and tumour cell proliferation in human epidermoid carcinoma Br J Cancer 73 931–934

    Google Scholar 

  24. KJ O’Byrne N Dobbs D Propper K Smith A Harris (1999) ArticleTitleVascular endothelial growth factor platelet counts, and prognosis in renal cancer Lancet 353 1494–1495

    Google Scholar 

  25. F Riedel K Gotte J Schwalb W Bergler K Hormann (2000) ArticleTitleExpression of 92-kDa type IV collagenase correlates with angiogenic markers and poor survival in head and neck squamous cell carcinoma Int J Oncol 17 1099–1105

    Google Scholar 

  26. R Salgado P Vermeulen I Benoy et al. (1999) ArticleTitlePlatelet number and interleukin-6 correlate with VEGF but not with bFGF serum levels of advanced cancer patients Br J Cancer 80 892–897

    Google Scholar 

  27. P Salven A Orpana H Joensuu (1999) ArticleTitleLeukocytes and platelets of patients with cancer contain high levels of vasular endothelial growth factor Clin Cancer Res 5 487–491

    Google Scholar 

  28. Y Shou T Hirano Y Gong et al. (2001) ArticleTitleInfluence of angiogenetic factors and matrix metalloproteinase upon tumour progression in non-small-cell lung cancer Br J Cancer 85 1706–1712

    Google Scholar 

  29. M Tamura Y Ohta T Kajita et al. (2001) ArticleTitlePlasma VEGF concentration can predict the tumor angiogenic capacity in non-small cell lung cancer Oncol Rep 8 1097–1102

    Google Scholar 

  30. H Verheul K Hoekman S Luykx-de Bakker et al. (1997) ArticleTitlePlatelet: transporter of vascular endothelial growth factor Clin Cancer Res 3 2187–2190

    Google Scholar 

  31. M Volm R Koomagi J Mateern T Efferth (2002) ArticleTitleProtein expression profile of primary human squamous cell lung carcinomas indicative of the incidence of metastases Clin Exp Metastasis 29 457–464

    Google Scholar 

  32. N Weidner J Folkman F Pozza (1992) ArticleTitleTumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma J Natl Cancer Inst 84 1875–1887

    Google Scholar 

  33. A Yuan CJ Yu WJ Chen et al. (2000) ArticleTitleCorrelation of total VEGF mRNA and protein expression with histologic type, tumor angiogenesis, patient survival and timing of relapse in non-small-cell lung cancer Int J Cancer 89 475–483

    Google Scholar 

Download references

Acknowlegments

We thank Kazue Shimizu for her excellent technical assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kazuhisa Takahashi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shimanuki, Y., Takahashi, K., Cui, R. et al. Role of Serum Vascular Endothelial Growth Factor in the Prediction of Angiogenesis and Prognosis for Non-small Cell Lung Cancer. Lung 183, 29–42 (2005). https://doi.org/10.1007/s00408-004-2521-4

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00408-004-2521-4

Keywords

Navigation