Skip to main content

Advertisement

SpringerLink
Log in

Correlation of Vascular Endothelial Growth Factor Expression With Tumor Recurrence and Poor Prognosis in Patients With pN0 Gastric Cancer

  • Published:
World Journal of Surgery Aims and scope Submit manuscript

Abstract

Background

Vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 play important roles in tumor angiogenesis, development, and progression. This study investigates the expression of VEGF combined with MMP-9, their correlation with clinical characteristics, and their effect on the prognosis for patients with pN0 gastric cancer after curative surgery.

Methods

A total of 55 patients were enrolled in the study. They were analyzed by immunohistochemistry, and their correlation with clinical characteristics was then investigated. Their relations and the survival time of patients were retrospectively analyzed.

Results

VEGF and MMP-9 were positively expressed in 24 (43.6%) and 16 (29.1%) patients, respectively, and had a positive correlation (r = 0.324, p = 0.016) in the Spearman rank correlation analysis. Univariate analysis showed that VEGF, MMP-9 expression, vascular invasion, T stage, and tumor size were associated with tumor recurrence as well as the disease-specific (DSS) and overall (OS) survival rates. Patients with positive VEGF expression showed significantly higher recurrence and poorer DSS and OS rates compared with those with negative VEGF expression. Multivariate analysis showed that VEGF expression, vascular invasion, T stage (serosal invasion), and tumor size were significant independent prognostic factors for tumor recurrence, DSS, and OS in patients with pN0 gastric cancer with the exception that T stage was not for DSS.

Conclusions

VEGF expression, vascular invasion, T stage (serosal invasion), and tumor size can be used as valuable prognosticators in predicting tumor recurrence and prognosis for patients with pN0 gastric cancer after curative surgery. VEGF may have a synergistic effect with MMP-9 during tumor angiogenesis, development, and progression.

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

Similar content being viewed by others

References

  1. Crew KD, Neugut AI (2006) Epidemiology of gastric cancer. World J Gastroenterol 12:354–362

    PubMed  Google Scholar 

  2. Leung DW, Cachianes G, Kuang WJ et al (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306–1309

    Article  PubMed  CAS  Google Scholar 

  3. Maeda K, Kang SM, Onoda N et al (1998) Expression of p53 and vascular endothelial growth factor associated with tumor angiogenesis and prognosis in gastric cancer. Oncology 55:594–599

    Article  PubMed  CAS  Google Scholar 

  4. Song ZJ, Gong P, Wu YE (2002) Relationship between the expression of iNOS, VEGF, tumor angiogenesis and gastric cancer. World J Gastroenterol 8:591–595

    PubMed  CAS  Google Scholar 

  5. Maeda K, Chung YS, Ogawa Y et al (1996) Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer 77:858–863

    Article  PubMed  CAS  Google Scholar 

  6. Vidal O, Soriano-Izquierdo A, Pera M et al (2008) Positive VEGF immunostaining independently predicts poor prognosis in curatively resected gastric cancer patients: results of a study assessing a panel of angiogenic markers. J Gastrointest Surg 12:1005–1014

    Article  PubMed  Google Scholar 

  7. Yasuda K, Adachi Y, Shiraishi N et al (2002) Prognostic effect of lymph node micrometastasis in patients with histologically node-negative gastric cancer. Ann Surg Oncol 9:771–774

    Article  PubMed  Google Scholar 

  8. Parikh RR, Yang Q, Haffty BG (2007) Prognostic significance of vascular endothelial growth factor protein levels in T1–2 N0 laryngeal cancer treated with primary radiation therapy. Cancer 109:566–573

    Article  PubMed  Google Scholar 

  9. Ogura S, Ohdaira T, Hozumi Y et al (2007) Metastasis-related factors expressed in pT1 pN0 breast cancer: assessment of recurrence risk. J Surg Oncol 96:46–53

    Article  PubMed  CAS  Google Scholar 

  10. Chien CY, Su CY, Hwang CF et al (2006) High expressions of CD105 and VEGF in early oral cancer predict potential cervical metastasis. J Surg Oncol 94:413–417

    Article  PubMed  CAS  Google Scholar 

  11. Green MM, Hiley CT, Shanks JH et al (2007) Expression of vascular endothelial growth factor (VEGF) in locally invasive prostate cancer is prognostic for radiotherapy outcome. Int J Radiat Oncol Biol Phys 67:84–90

    Article  PubMed  CAS  Google Scholar 

  12. Herszenyi L, Sipos F, Galamb O et al (2008) Matrix metalloproteinase-9 expression in the normal mucosa-adenoma-dysplasia-adenocarcinoma sequence of the colon. Pathol Oncol Res 14:31–37

    Article  PubMed  CAS  Google Scholar 

  13. Zheng H, Takahashi H, Murai Y et al (2006) Expressions of MMP-2, MMP-9 and VEGF are closely linked to growth, invasion, metastasis and angiogenesis of gastric carcinoma. Anticancer Res 26:3579–3583

    PubMed  CAS  Google Scholar 

  14. Gao ZL, Zhang C, Du GY et al (2007) Clinical significance of changes in tumor markers, extracellular matrix, MMP-9 and VEGF in patients with gastric carcinoma. Hepatogastroenterology 54:1591–1595

    PubMed  CAS  Google Scholar 

  15. Tamura M, Oda M, Matsumoto I et al (2004) The combination assay with circulating vascular endothelial growth factor (VEGF)-C, matrix metalloproteinase-9, and VEGF for diagnosing lymph node metastasis in patients with non-small cell lung cancer. Ann Surg Oncol 11:928–933

    Article  PubMed  Google Scholar 

  16. Hao L, Zhang C, Qiu Y et al (2007) Recombination of CXCR4, VEGF, and MMP-9 predicting lymph node metastasis in human breast cancer. Cancer Lett 253:34–42

    Article  PubMed  CAS  Google Scholar 

  17. Weidner N (1995) Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat 36:169–180

    Article  PubMed  CAS  Google Scholar 

  18. Zhang S, Li L, Lin JY et al (2003) Imbalance between expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in invasiveness and metastasis of human gastric carcinoma. World J Gastroenterol 9:899–904

    PubMed  CAS  Google Scholar 

  19. Kim DY, Seo KW, Joo JK et al (2006) Prognostic factors in patients with node-negative gastric carcinoma: a comparison with node-positive gastric carcinoma. World J Gastroenterol 12:1182–1186

    PubMed  Google Scholar 

  20. Kwon SJ, Kim GS (1996) Prognostic significance of lymph node metastasis in advanced carcinoma of the stomach. Br J Surg 83:1600–1603

    Article  PubMed  CAS  Google Scholar 

  21. Ohgaki M, Toshio T, Akeo H et al (1999) Effect of extensive lymph node dissection on the survival of early gastric cancer. Hepatogastroenterology 46:2096–2099

    PubMed  CAS  Google Scholar 

  22. Kaneko T, Konno H, Baba M et al (2003) Urokinase-type plasminogen activator expression correlates with tumor angiogenesis and poor outcome in gastric cancer. Cancer Sci 94:43–49

    Article  PubMed  CAS  Google Scholar 

  23. Yu HG, Li JY, Yang YN et al (2003) Increased abundance of cyclooxygenase-2 correlates with vascular endothelial growth factor-A abundance and tumor angiogenesis in gastric cancer. Cancer Lett 195:43–51

    Article  PubMed  CAS  Google Scholar 

  24. Ma J, Zhang L, Ru GQ et al (2007) Upregulation of hypoxia inducible factor 1alpha mRNA is associated with elevated vascular endothelial growth factor expression and excessive angiogenesis and predicts a poor prognosis in gastric carcinoma. World J Gastroenterol 13:1680–1686

    PubMed  CAS  Google Scholar 

  25. Maeda K, Chung YS, Takatsuka S et al (1995) Tumor angiogenesis as a predictor of recurrence in gastric carcinoma. J Clin Oncol 13:477–481

    PubMed  CAS  Google Scholar 

  26. Alexandrakis MG, Sfiridaki A, Miyakis S et al (2007) Relationship between serum levels of vascular endothelial growth factor, hepatocyte growth factor and matrix metalloproteinase-9 with biochemical markers of bone disease in multiple myeloma. Clin Chim Acta 379:31–35

    Article  PubMed  CAS  Google Scholar 

  27. Guo RP, Zhong C, Shi M et al (2006) Clinical value of apoptosis and angiogenesis factors in estimating the prognosis of hepatocellular carcinoma. J Cancer Res Clin Oncol 132:547–555

    Article  PubMed  CAS  Google Scholar 

  28. Liu CJ, Chang KW, Lin SC et al (2009) Presurgical serum levels of matrix metalloproteinase-9 and vascular endothelial growth factor in oral squamous cell carcinoma. Oral Oncol 45:920–925

    Article  PubMed  CAS  Google Scholar 

  29. Janowska-Wieczorek A, Majka M, Marquez-Curtis L et al (2002) Bcr-abl-positive cells secrete angiogenic factors including matrix metalloproteinases and stimulate angiogenesis in vivo in Matrigel implants. Leukemia 16:1160–1166

    Article  PubMed  CAS  Google Scholar 

  30. Dias S, Hattori K, Zhu Z et al (2000) Autocrine stimulation of VEGFR-2 activates human leukemic cell growth and migration. J Clin Invest 106:511–521

    Article  PubMed  CAS  Google Scholar 

  31. Owen JL, Iragavarapu-Charyulu V, Gunja-Smith Z et al (2003) Up-regulation of matrix metalloproteinase-9 in T lymphocytes of mammary tumor bearers: role of vascular endothelial growth factor. J Immunol 171:4340–4351

    PubMed  CAS  Google Scholar 

  32. Zhao R, Liu XQ, Wu XP et al (2010) Vascular endothelial growth factor (VEGF) enhances gastric carcinoma invasiveness via integrin alpha(v)beta6. Cancer Lett 287:150–156

    Article  PubMed  CAS  Google Scholar 

  33. Bergers G, Brekken R, McMahon G et al (2000) Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2:737–744

    Article  PubMed  CAS  Google Scholar 

  34. Belotti D, Paganoni P, Manenti L et al (2003) Matrix metalloproteinases (MMP9 and MMP2) induce the release of vascular endothelial growth factor (VEGF) by ovarian carcinoma cells: implications for ascites formation. Cancer Res 63:5224–5229

    PubMed  CAS  Google Scholar 

  35. Hawinkels LJ, Zuidwijk K, Verspaget HW et al (2008) VEGF release by MMP-9 mediated heparan sulphate cleavage induces colorectal cancer angiogenesis. Eur J Cancer 44:1904–1913

    Article  PubMed  CAS  Google Scholar 

  36. Mori M, Sugimachi K (1990) Clinicopathologic studies of gastric carcinoma. Semin Surg Oncol 6:19–27

    Article  PubMed  CAS  Google Scholar 

  37. Kooby DA, Suriawinata A, Klimstra DS et al (2003) Biologic predictors of survival in node-negative gastric cancer. Ann Surg 237:828–835; discussion 835–837

    PubMed  Google Scholar 

Download references

Acknowledgments

We are indebted to Dr. Shu-hai Li and Lu-tao Du (School of Medicine, Shandong University) for their excellent statistical work. We are also grateful to Dr. Jin-song Li and Meng Chen (Department of Pathology, Qilu Hospital, Shandong University) for their technical assistance.

Conflict of interest

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Qilu Hospital, Shandong University, 107#, Wenhua Xi Road, Jinan, 250012, China

    Yan-feng Liu, Sen Guo, Rui Zhao & Ke-sen Xu

  2. Department of General Surgery, Qilu Hospital, Shandong University, 107#, Wenhua Xi Road, Jinan, 250012, China

    Yue-guang Chen & Xian-qiang Wang

Authors
  1. Yan-feng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sen Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rui Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yue-guang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xian-qiang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ke-sen Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ke-sen Xu.

Additional information

The first two authors contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, Yf., Guo, S., Zhao, R. et al. Correlation of Vascular Endothelial Growth Factor Expression With Tumor Recurrence and Poor Prognosis in Patients With pN0 Gastric Cancer. World J Surg 36, 109–117 (2012). https://doi.org/10.1007/s00268-011-1192-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00268-011-1192-6

Keywords

Search

Navigation