Skip to main content

Advertisement

Log in

Serum VEGF and VEGF-C values before surgery and after postoperative treatment in gastric cancer

  • Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Introduction

Angiogenesis and lymphangiogenesis are essential processes for the formation of blood and lymphatic vessels that allow tumour growth and spread. The binding of VEGF and VEGF-C factors with their receptors (VEGFR2, VEGFR3) in endothelial cells triggers signals that regulate these processes. We compared preoperative serum VEGF and VEGF-C levels with samples obtained after completion of surgery and adjuvant treatment in patients with gastric cancer. In addition, we determined the prognostic value and relationship to survival of serum VEGF and VEGF-C levels.

Methods

We used a prospective cohort study of 59 gastric cancer patients who underwent surgery. Serum VEGF and VEGF-C were measured by enzyme-linked immunosorbent assay (ELISA) the day before surgery and 6 months later, after completion of adjuvant treatment.

Results

Serum VEGF values decreased after treatment in patients with resectable tumours (mean ± SD) (405.42 ± 298.38 vs. 306.38 ± 212.47 pg/ml; p < 0.01), poorly differentiated and undifferentiated tumours (G3, G4) (438 ± 339.71 vs. 322.47 ± 210.71 pg/ml; p = 0.01), locally advanced gastric tumours (T4 stage) (424.27 ± 323.08 vs. 333.62 ± 221.72 pg/ml; p = 0.03) and tumours with a greater number of involved regional lymph nodes (N3) (442.38 ± 311.52 vs. 337.4 ± 203.64 pg/ml; p = 0.04). Serum preoperative VEGF values over 761 pg/ml were associated with shorter patient survival. The mean overall survival time for patients with serum VEGF levels higher than 761 pg/ml was 7 ± 2.99 months (95 % CI 1.14–12.86) while for patients with serum VEGF levels of less than 761 pg/ml was 21.18 ± 2.88 (95 % CI 15.54–26.83) The mean disease-specific survival time for patients with serum VEGF levels higher than 761 pg/ml was 6.25 ± 2.53 months (95 % CI 1.29–11.21) while for patients with serum VEGF levels of less than 761 pg/ml was 27.57 ± 3.45 (95 % CI 20.80–34.35). Multivariate analysis identified preoperative serum VEGF levels as an independent prognostic factor (HR = 0.144; p = 0.03).

Conclusions

Serum VEGF levels decreased after the completion of treatment in patients with resected tumours, suggesting VEGF tracking may be useful in monitoring progression. Preoperative measurement of serum VEGF may help us identify patients with a poor prognosis.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Folkman J (1992) The role of angiogenesis in tumor growth. Semin Cancer Biol 3:65–71

    PubMed  CAS  Google Scholar 

  2. Cheong JH, Hong SY, Zheng Y, Noh SH (2011) Eupatilin inhibits gastric cancer cell growth by blocking STAT3-mediated VEGF expression. J Gastric Cancer 11:16–22

    Article  PubMed  Google Scholar 

  3. Osinsky S, Bubnovskaya L, Ganusevich I, Kovelskaya A, Gumenyuk L, Olijnichenko G et al (2011) Hypoxia, tumour-associated macrophages, microvessel density, VEGF and matrix metalloproteinases in human gastric cancer: interaction and impact on survival. Clin Transl Oncol 13:133–138

    Article  PubMed  CAS  Google Scholar 

  4. Christopoulos A, Ahn SM, Klein JD, Kim S (2011) Biology of vascular endothelial growth factor and its receptors in head and neck cancer: beyond angiogenesis. Head Neck 33:1220–1229

    Article  PubMed  Google Scholar 

  5. Al-Rawi MA, Mansel RE, Jiang WG (2005) Molecular and cellular mechanisms of lymphangiogenesis. Eur J Surg Oncol 31:117–121

    Article  PubMed  CAS  Google Scholar 

  6. Nagahashi M, Ramachandran S, Rashid OM, Takabe K (2010) Lymphangiogenesis: a new player in cancer progression. World J Gastroenterol 16:4003–4012

    Article  PubMed  CAS  Google Scholar 

  7. Fondevila C, Metges JP, Fuster J, Grau JJ, Palacin A, Castells A et al (2004) p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer. Br J Cancer 90:206–215

    Article  PubMed  CAS  Google Scholar 

  8. Chen J, Li T, Wu Y, He L, Zhang L, Shi T et al (2011) Prognostic significance of vascular endothelial growth factor expression in gastric carcinoma: a meta-analysis. J Cancer Res Clin Oncol 137:1799–1812

    Article  PubMed  CAS  Google Scholar 

  9. Duff SE, Li C, Jeziorska M, Kumar S, Saunders MP, Sherlock D et al (2003) Vascular endothelial growth factors C and D and lymphangiogenesis in gastrointestinal tract malignancy. Br J Cancer 89:426–430

    Article  PubMed  CAS  Google Scholar 

  10. Han FH, Li HM, Zheng DH, He YL, Zhan WH (2010) The effect of the expression of vascular endothelial growth factor (VEGF)-C and VEGF receptor-3 on the clinical outcome in patients with gastric carcinoma. Eur J Surg Oncol 36:1172–1179

    Article  PubMed  Google Scholar 

  11. Ding S, Lin S, Dong X, Yang X, Qu H, Huang S et al (2005) Potential prognostic value of circulating levels of vascular endothelial growth factor-A in patients with gastric cancer. In Vivo (Athens, Greece) 19:793–795

    CAS  Google Scholar 

  12. Werther K, Christensen IJ, Nielsen HJ (2002) Prognostic impact of matched preoperative plasma and serum VEGF in patients with primary colorectal carcinoma. Br J Cancer 86:417–423

    Article  PubMed  CAS  Google Scholar 

  13. Bouvier AM, Sant M, Verdecchia A, Forman D, Damhuis R, Willem Coebergh J et al (2010) What reasons lie behind long-term survival differences for gastric cancer within Europe? Eur J Cancer 46:1086–1092

    Article  PubMed  Google Scholar 

  14. Bentrem D, Gerdes H, Tang L, Brennan M, Coit D (2007) Clinical correlation of endoscopic ultrasonography with pathologic stage and outcome in patients undergoing curative resection for gastric cancer. Ann Surg Oncol 14:1853–1859

    Article  PubMed  Google Scholar 

  15. Washington K (2010) 7th edition of the AJCC cancer staging manual: stomach. Ann Surg Oncol 17:3077–3079

    Article  PubMed  Google Scholar 

  16. Mazumdar M, Smith A, Bacik J (2003) Methods for categorizing a prognostic variable in a multivariable setting. Stat Med 22:559–571

    Article  PubMed  Google Scholar 

  17. De Vita F, Orditura M, Lieto E, Infusino S, Morgillo F, Martinelli E et al (2004) Elevated perioperative serum vascular endothelial growth factor levels in patients with colon carcinoma. Cancer 100:270–278

    Article  PubMed  Google Scholar 

  18. Karayiannakis AJ, Bolanaki H, Syrigos KN, Asimakopoulos B, Polychronidis A, Anagnostoulis S et al (2003) Serum vascular endothelial growth factor levels in pancreatic cancer patients correlate with advanced and metastatic disease and poor prognosis. Cancer Lett 194:119–124

    Article  PubMed  CAS  Google Scholar 

  19. Schoenleber SJ, Kurtz DM, Talwalkar JA, Roberts LR, Gores GJ (2004) Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and meta-analysis. Br J Cancer 100:1385–1392

    Article  Google Scholar 

  20. Carrillo-de Santa Pau E, Carrillo Arias F, Caso Pelaez E, Muguruza Trueba I, Sanchez Hernandez I, Munoz Molina GM et al (2009) Vascular endothelial growth factor (VEGF) serum levels are associated with survival in early stages of lung cancer patients. Cancer Invest 28:393–398

    Google Scholar 

  21. Zusterzeel PL, Span PN, Dijksterhuis MG, Thomas CM, Sweep FC, Massuger LF (2009) Serum vascular endothelial growth factor: a prognostic factor in cervical cancer. J Cancer Res Clin Oncol 135:283–290

    Article  PubMed  CAS  Google Scholar 

  22. Vidal O, Metges JP, Elizalde I, Valentini M, Volant A, Molina R et al (2009) High preoperative serum vascular endothelial growth factor levels predict poor clinical outcome after curative resection of gastric cancer. Br J Surg 96:1443–1451

    Article  PubMed  CAS  Google Scholar 

  23. Karayiannakis AJ, Syrigos KN, Polychronidis A, Zbar A, Kouraklis G, Simopoulos C et al (2002) Circulating VEGF levels in the serum of gastric cancer patients: correlation with pathological variables, patient survival, and tumor surgery. Ann Surg 236:37–42

    Article  PubMed  Google Scholar 

  24. Tamura M, Ohta Y (2003) Serum vascular endothelial growth factor-C level in patients with primary nonsmall cell lung carcinoma: a possible diagnostic tool for lymph node metastasis. Cancer 98(6):1217–1222

    Article  PubMed  CAS  Google Scholar 

  25. Yu XM, Lo CY, Lam AK, Leung P, Luk JM (2008) Serum vascular endothelial growth factor C correlates with lymph node metastases and high-risk tumor profiles in papillary thyroid carcinoma. Ann Surg 247:483–489

    Article  PubMed  Google Scholar 

  26. Krzystek-Korpacka M, Matusiewicz M, Diakowska D, Grabowski K, Blachut K, Banas T (2007) Up-regulation of VEGF-C secreted by cancer cells and not VEGF-A correlates with clinical evaluation of lymph node metastasis in esophageal squamous cell carcinoma (ESCC). Cancer Lett 249:171–177

    Article  PubMed  CAS  Google Scholar 

  27. Wang TB, Deng MH, Qiu WS, Dong WG (2007) Association of serum vascular endothelial growth factor-C and lymphatic vessel density with lymph node metastasis and prognosis of patients with gastric cancer. World J Gastroenterol 13:1794–1797

    PubMed  CAS  Google Scholar 

  28. Bogos K, Renyi-Vamos F, Dobos J, Kenessey I, Tovari J, Timar J et al (2009) High VEGFR-3-positive circulating lymphatic/vascular endothelial progenitor cell level is associated with poor prognosis in human small cell lung cancer. Clin Cancer Res 15:1741–1746

    Article  PubMed  CAS  Google Scholar 

  29. Alabi AA, Suppiah A, Madden LA, Monson JR, Greenman J (2009) Preoperative serum levels of serum VEGF-C is associated with distant metastasis in colorectal cancer patients. Int J Colorectal Dis 24:269–274

    Article  PubMed  Google Scholar 

  30. Sung JY, Lee S, Kim YW, Park YK (2008) Vascular endothelial growth factor receptor-3 is a favorable prognostic factor in advanced gastric carcinoma. Oncol Rep 19:939–944

    PubMed  Google Scholar 

  31. Mouawad R, Spano JP, Comperat E, Capron F, Khayat D (2009) Tumoural expression and circulating level of VEGFR-3 (Flt-4) in metastatic melanoma patients: correlation with clinical parameters and outcome. Eur J Cancer 45:1407–1414

    Article  PubMed  CAS  Google Scholar 

  32. Kirk R (2011) Targeted therapies: should we be aghast at the AVAGAST data? Nat Rev Clin Oncol 8:567

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Pedro Villarejo-Campos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Villarejo-Campos, P., Padilla-Valverde, D., Martin, R.M. et al. Serum VEGF and VEGF-C values before surgery and after postoperative treatment in gastric cancer. Clin Transl Oncol 15, 265–270 (2013). https://doi.org/10.1007/s12094-012-0908-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-012-0908-x

Keywords

Navigation