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Prognostic Values of VEGF and Endostatin with Malignant Pleural Effusions in Patients with Lung Cancer

  • Zhang, Yu (First Department of Respiratory Medicine, Nanjing Chest Hospital) ;
  • Yu, Li-Ke (First Department of Respiratory Medicine, Nanjing Chest Hospital) ;
  • Lu, Guo-Jun (First Department of Respiratory Medicine, Nanjing Chest Hospital) ;
  • Xia, Ning (First Department of Respiratory Medicine, Nanjing Chest Hospital) ;
  • Xie, Hai-Yan (First Department of Respiratory Medicine, Nanjing Chest Hospital) ;
  • Hu, Wei (First Department of Respiratory Medicine, Nanjing Chest Hospital) ;
  • Hao, Ke-Ke (First Department of Respiratory Medicine, Nanjing Chest Hospital) ;
  • Xu, Chun-Hua (First Department of Respiratory Medicine, Nanjing Chest Hospital) ;
  • Qian, Qian (First Department of Respiratory Medicine, Nanjing Chest Hospital)
  • Published : 2014.10.23

Abstract

Aims: Angiogenesis is important in malignant pleural effusion (MPE) formation and it is regulated by a number of pro- and anti-angiogenic cytokines. The purpose of this study was to evaluate the prognostic value of angiogenic factor vascular endothelial growth factor (VEGF) and angiogenesis inhibitor endostatin in lung cancer patients with MPE, and investigate the relationship between these two kinds of agent. Methods: Using enzyme-linked immunoadsorbent assay, the concentrations of VEGF and endostatin were measured in pleural effusions (PE) and serum from a total of 70 lung cancer patients with MPE and 20 patients with tuberculosis. Results: Compared to patients with tuberculosis, the levels of VEGF and endostatin in both PE and serum were significantly higher in patients with lung cancer. There were statistically significant correlations between VEGF levels in PE and serum (r=0.696, p<0.001), endostatin levels in PE and serum (r=0.310, p=0.022), and VEGF and endostatin levels in PE (r=0.287, p=0.019). Cox multivariate analysis revealed that elevated pleural VEGF and endostatin levels and serum endostatin level were independent predictors of shorter overall survival. Conclusion: Both pro- and anti-angiogenic factors are likely contributors to PE formation. Our results suggest that the levels of VEGF and endostatin in PE, together with endostatin in serum, may be potential prognostic parameters for lung cancer patients with MPE.

Keywords

Malignant pleural effusion;lung cancer;prognosis;vascular endothelial growth factor;endostatin

Acknowledgement

Supported by : Nanjing Medical Science and Technique Development Foundation

References

  1. Chakra M, Pujol JL, Lamy PJ, et al (2008). Circulating serum vascular endothelial growth factor is not a prognostic factor of non-small cell lung cancer. J Thorac Oncol, 3, 1119-26. https://doi.org/10.1097/JTO.0b013e318187464e
  2. Bradshaw M, Mansfield A, Peikert T (2013). The role of vascular endothelial growth factor in the pathogenesis, diagnosis and treatment of malignant pleural effusion. Curr Oncol Rep, 15, 207-16. https://doi.org/10.1007/s11912-013-0315-7
  3. Davies H E, Lee Y C G (2013). Management of malignant pleural effusions: questions that need answers. Curr Opin Pulm Med, 19, 374-9. https://doi.org/10.1097/MCP.0b013e3283615b67
  4. Chen X, Liu Y, Yin Y, et al (2012). Recombinant human endostatin (endostar) decreased recurrent ascites, pleural fluid and ascitic VEGF in a case of advanced mesothelioma. J Chemother, 24, 231-6. https://doi.org/10.1179/1973947812Y.0000000023
  5. Chen Y, Liang B, Zhao Y J, et al (2012). Transcription expression and clinical significance of vascular endothelial growth factor mRNA and endostatin mRNA in pleural effusions of patients with lung cancer. Diagn Cytopathol, 40, 287-91. https://doi.org/10.1002/dc.21546
  6. Choi J H, Chul Kim H, Lim H Y, et al (2001). Vascular endothelial growth factor in the serum of patients with nonsmall cell lung cancer: correlation with platelet and leukocyte counts. Lung Cancer, 33, 171-79. https://doi.org/10.1016/S0169-5002(01)00200-8
  7. Dong XP, Xiao TH, Dong H, et al (2013). Endostar combined with cisplatin inhibits tumor growth and lymphatic metastasis of lewis lung carcinoma xenografts in mice. Asian Pac J Cancer Prev, 14, 3079-83. https://doi.org/10.7314/APJCP.2013.14.5.3079
  8. Du N, Li X, Li F, et aln (2013). Intrapleural combination therapy with bevacizumab and cisplatin for non-small cell lung cancer-mediated malignant pleural effusion. Oncol Rep, 29, 2332-40.
  9. Fiorelli A, Vicidomini G, Di Domenico M, et al (2011). Vascular endothelial growth factor in pleural fluid for differential diagnosis of benign and malignant origin and its clinical applications. Interact Cardiovasc Thorac Surg, 12, 420-4. https://doi.org/10.1510/icvts.2010.250357
  10. Goldstraw P, Crowley J, Chansky K, et al (2007). The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol, 2, 706-14. https://doi.org/10.1097/JTO.0b013e31812f3c1a
  11. Hsu I L, Su WC, Yan JJ, et al (2009). Angiogenetic biomarkers in non-small cell lung cancer with malignant pleural effusion: correlations with patient survival and pleural effusion control. Lung Cancer, 65, 371-6. https://doi.org/10.1016/j.lungcan.2008.12.007
  12. Hama M, Komatsu Y, Hachiya T (2011). A case of lung cancer showing marked reduction of pleural effusion by bevacizumab in combination with carboplatin and paclitaxel. Gan to kagaku ryoho. Gan To Kagaku Ryoho, 38, 1877-9.
  13. Hasegawa Y, Takanashi S, Okudera K, et al (2005). Vascular endothelial growth factor level as a prognostic determinant of small cell lung cancer in Japanese patients. Intern Med (Tokyo, Japan), 44, 26-4. https://doi.org/10.2169/internalmedicine.44.26
  14. Heffner JE (2008). Diagnosis and management of malignant pleural effusions. Respirology, 13, 5-20.
  15. Iizasa T, Chang H, Suzuki M, et al (2004). Overexpression of Collagen XVIII is associated with poor outcome and elevated levels of circulating serum endostatin in non-small cell lung cancer. Clin Cancer Res, 10, 5361-6. https://doi.org/10.1158/1078-0432.CCR-04-0443
  16. Ishimoto O, Saijo Y, Narumi K, et al (2002). High level of vascular endothelial growth factor in hemorrhagic pleural effusion of cancer. Oncology, 63, 70-5. https://doi.org/10.1159/000065723
  17. Kaya A, Ciledag A, Gulbay B E, et al (2004). The prognostic significance of vascular endothelial growth factor levels in sera of non-small cell lung cancer patients. Respir Med, 98, 632-6. https://doi.org/10.1016/j.rmed.2003.12.017
  18. Kitamura K, Kubota K, Ando M, et al (2013). Bevacizumab plus chemotherapy for advanced non-squamous non-smallcell lung cancer with malignant pleural effusion. Cancer Chemother Pharmacol, 71, 457-61. https://doi.org/10.1007/s00280-012-2026-4
  19. Koniari I, Koletti B, Apostolakis E (2011). Vascular endothelial growth factor with tumour growth factor-${\beta}$, endostatin, proteinases or cytokines might be useful for differential diagnosis of pleural effusions. Interact Cardiovasc Thorac Surg, 12, 424-5. https://doi.org/10.1510/icvts.2010.250357A
  20. Memon A, Zawadzki Z A (1981). Malignant effusions: diagnostic evaluation and therapeutic strategy. Curr Probl Cancer, 5, 1-30.
  21. Laack E, Kohler A, Kugler C, et al (2002). Pretreatment serum levels of matrix metalloproteinase-9 and vascular endothelial growth factor in non-small-cell lung cancer. Ann Oncol, 13, 1550-7. https://doi.org/10.1093/annonc/mdf270
  22. Ma X, Yao Y, Yuan D, et al (2012). Recombinant human endostatin endostar suppresses angiogenesis and lymphangiogenesis of malignant pleural effusion in mice. PloS One, 7, e53449. https://doi.org/10.1371/journal.pone.0053449
  23. Macchiarini P, Fontanini G, Squartini F, et al (1992). Relation of neovascularisation to metastasis of non-small-cell lung cancer. Lancet, 340, 145-6. https://doi.org/10.1016/0140-6736(92)93217-B
  24. O'Reilly M S, Boehm T, Shing Y, et al (1997). Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell, 88, 277-85. https://doi.org/10.1016/S0092-8674(00)81848-6
  25. Roberts M E, Neville E, Berrisford R G, et al (2010). Management of a malignant pleural effusion: British Thoracic Society pleural disease guideline 2010. Thorax, 65, ii32-0.
  26. Ruiz E, Aleman C, Alegre J, et al (2005). Angiogenic factors and angiogenesis inhibitors in exudative pleural effusions. Lung, 183, 185-95. https://doi.org/10.1007/s00408-004-2533-0
  27. Sack U, Hoffmann M, Zhao XJ, et al (2005). Vascular endothelial growth factor in pleural effusions of different origin. Eur Respir J, 25, 600-04. https://doi.org/10.1183/09031936.05.00037004
  28. Salven P, Orpana A, Joensuu H (1999). Leukocytes and platelets of patients with cancer contain high levels of vascular endothelial growth factor. Clin Cancer Res, 5, 487-91.
  29. Skovseth D K, Veuger M J T, Sorensen D R, et al (2005). Endostatin dramatically inhibits endothelial cell migration, vascular morphogenesis, and perivascular cell recruitment in vivo. Blood, 105, 1044-51.
  30. Yanagawa H, Takeuchi E, Suzuki Y, et al (1999). Vascular endothelial growth factor in malignant pleural effusion associated with lung cancer. Cancer Immunol Immunother, 48, 396-00. https://doi.org/10.1007/s002620050592
  31. Song XY, Zhou SJ, Xiao N, et al (2013). Research on the relationship between serum levels of inflammatory cytokines and non-small cell lung cancer. Asian Pac J Cancer Prev, 14, 4765-8. https://doi.org/10.7314/APJCP.2013.14.8.4765
  32. Sumi M, Kagohashi K, Satoh H, et al (2003). Endostatin levels in exudative pleural effusions. Lung, 181, 329-34. https://doi.org/10.1007/s00408-003-1035-9
  33. Suzuki M, Iizasa T, Ko E, et al (2002). Serum endostatin correlates with progression and prognosis of non-small cell lung cancer. Lung Cancer, 35, 29-4. https://doi.org/10.1016/S0169-5002(01)00285-9
  34. Zebrowski BK, Yano S, Liu W, et al (1999). Vascular endothelial growth factor levels and induction of permeability in malignant pleural effusions. Clin Cancer Res, 5, 3364-8.
  35. Zhang Y, Yu LK, Xia N (2012). Evaluation of serum and pleural levels of endostatin and vascular epithelial growth factor in lung cancer patients with pleural effusion. Asian Pac J Trop Med, 5, 239-42. https://doi.org/10.1016/S1995-7645(12)60032-7
  36. Zhou WB, Bai M, Jin Y (2009). Diagnostic value of vascular endothelial growth factor and endostatin in malignant pleural effusions. Int J Tuberc Lung Dis, 13, 381-6.
  37. Ziora D, Sielska-Spytek E, Dworniczak S, et al (2002). VEGF (vascular endothelial growth factor) concentration in serum and pleural fluid of patients with pleural malignancy and pleural tuberculosis. Pneumonol Alergol Pol, 70, 458-67.

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