Expression of Epidermal Growth Factor-like Domain 7 is Increased by Transcatheter Arterial Embolization of Liver Tumors

  • Li, Zhi (Department of Interventional Radiology, the First Affiliated Hospital of Soochow University) ;
  • Ni, Cai-Fang (Department of Interventional Radiology, the First Affiliated Hospital of Soochow University) ;
  • Zhou, Jin (Department of General Surgery, the First Affiliated Hospital of Soochow University) ;
  • Shen, Xiao-Chun (Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University) ;
  • Yin, Yu (Department of Interventional Radiology, the First Affiliated Hospital of Soochow University) ;
  • Du, Peng (Department of Interventional Radiology, the First Affiliated Hospital of Soochow University) ;
  • Yang, Chao (Department of Interventional Radiology, the First Affiliated Hospital of Soochow University)
  • Published : 2015.03.04


Background: Epidermal growth factor-like domain multiple 7 (EGFL7), recently identified as a secreted protein regulated by oxygen exposure, plays a critical role in promoting metastasis of hepatocellular carcinoma (HCC). Transcatheter arterial embolization (TAE) is widely used for treatment of HCC, resulting in hypoxia in tumors and surrounding liver tissues. Accordingly, we proposed the hypothesis that there could be a relationship between expression of EGFL7 and response to TAE. Materials and Methods: We established a rabbit VX2 liver tumor model using percutaneous puncture technique guided by computed tomography. TAE and sham embolization were performed and the results were confirmed by MRI 3 weeks after inoculation. We investigated the EGFL7 expression of the two groups at 6h and 3 days after intervention by means of immunohistochemistry and Western blotting. Results: Immunohistochemical staining demonstrated that the levels of EGFL7 protein significantly increased in the TAE-treated tumors compared with the control group at 6 hours (P=0.031) and 3 days (P=0.020) after intervention. Meanwhile, the relative EGFL7 protein detected in TAE group also up-regulated compared with the control group at 6 hours (P=0.020) and 3 days (P=0.024) after intervention. Conclusions: This study reveals an increase of EGFL7 expression in rabbit VX2 liver tumors after TAE. The role of EGFL7 in HCC, especially its biological behavior after TAE, needs further investigation.


Supported by : National Science Foundation of China


  1. Abdelaziz AO, Elbaz TM, Shousha HI, et al (2014). Survival and prognostic factors for hepatocellular carcinoma: an Egyptian multidisciplinary clinic experience. Asian Pac J Cancer Prev, 15, 3915-20.
  2. Badiwala MV, Tumiati LC, Joseph JM, et al (2010). Epidermal growth factor-like domain 7 suppresses intercellular adhesion molecule 1 expression in response to hypoxia/reoxygenation injury in human coronary artery endothelial cells. Circulation, 122, 156-61.
  3. Chung YH, Han G, Yoon JH, et al (2013). Interim analysis of START: Study in Asia of the combination of TACE (transcatheter arterial chemoembolization) with sorafenib in patients with hepatocellular carcinoma trial. Int J Cancer, 132, 2448-58.
  4. Dai XZ, Yin HT, Sun LF, et al (2013).Potential therapeutic efficacy of curcumin in liver cancer. Asian Pac J Cancer Prev, 14, 3855-9.
  5. Delfortrie S, Pinte S, Mattot V, et al (2011). Egfl7 promotes tumor escape from immunity by repressing endothelial cell activation. Cancer Res, 71, 7176-86.
  6. Diaz R, Silva J, Garcia JM, et al (2008). Deregulated expression of miR-106a predicts survival in human colon cancer patients. Genes Chromosomes Cancer, 47, 794-802.
  7. Fan C, Yang LY, Wu F, et al (2013). The expression of Egfl7 in human normal tissues and epithelial tumors. Int J Biol Markers, 28, 71-83.
  8. Farazi PA, DePinho RA (2006). Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer, 6, 674-87.
  9. Forner A, Llovet JM, Bruix J (2012). Hepatocellular carcinoma. Lancet, 379, 1245-55.
  10. Han G, Yang J, Shao G, et al (2013). Sorafenib in combination with transarterial chemoembolization in Chinese patients with hepatocellular carcinoma: a subgroup interim analysis of the START trial. Future Oncol, 9, 403-10.
  11. Hsieh MY, Lin ZY, Chuang WL (2011). Serial serum VEGF-A, angiopoietin-2, and endostatin measurements in cirrhotic patients with hepatocellular carcinoma treated by transcatheter arterial chemoembolization. Kaohsiung J Med Sci, 27, 314-22.
  12. Huang CH, Li XJ, Zhou YZ, et al (2010). Expression and clinical significance of EGFL7 in malignant glioma. J Cancer Res Clin Oncol, 136, 1737-43.
  13. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90.
  14. Lai JP, Conley A, Knudsen BS, et al (2014). Hypoxia after transarterial chemoembolization (TACE) may trigger a progenitor cell phenotype in hepatocellular carcinoma (HCC). Histopathology.
  15. Lelievre E, Hinek A, Lupu F, et al (2008). VE-statin/egfl7 regulates vascular elastogenesis by interacting with lysyl oxidases. Embo J, 27, 1658-70.
  16. Lewandowski RJ, Wang D, Gehl J, et al (2007). A comparison of chemoembolization endpoints using angiographic versus transcatheter intraarterial perfusion/MR imaging monitoring. J Vasc Interv Radiol, 18, 1249-57.
  17. Liou TC, Shih SC, Kao CR, et al (1995). Pulmonary metastasis of hepatocellular carcinoma associated with transarterial chemoembolization. J Hepatol, 23, 563-8.
  18. Liu WG, Gu WZ, Zhou YB, et al (2008). The prognostic relevance of preoperative transcatheter arterial chemoembolization (TACE) and PCNA/VEGF expression in patients with Wilms' tumour. Eur J Clin Invest, 38, 931-38.
  19. Llovet JM, Bruix J (2003). Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology, 37, 429-42.
  20. Mao YM, Luo ZY, Li B, et al (2012). Prospective study on the survival of HCC patients treated with transcatheter arterial lipiodol chemoembolization. Asian Pac J Cancer Prev, 13, 1039-42.
  21. Nichol D, Stuhlmann H (2012). EGFL7: a unique angiogenic signaling factor in vascular development and disease. Blood, 119, 1345-52.
  22. Parker LH, Schmidt M, Jin SW, et al (2004). The endothelial-cell-derived secreted factor Egfl7 regulates vascular tube formation. Nature, 428, 754-8.
  23. Parvinian A, Casadaban LC, Gaba RC (2014). Development, growth, propagation, and angiographic utilization of the rabbit VX2 model of liver cancer: a pictorial primer and “how to” guide. Diagn Interv Radiol, 20, 335-40.
  24. Sasaki A, Iwashita Y, Shibata K, et al (2006). Preoperative transcatheter arterial chemoembolization reduces longterm survival rate after hepatic resection for resectable hepatocellular carcinoma. Eur J Surg Oncol, 32, 773-9.
  25. Shim JH, Park JW, Kim JH, et al (2008). Association between increment of serum VEGF level and prognosis after transcatheter arterial chemoembolization in hepatocellular carcinoma patients. Cancer Sci, 99, 2037-44.
  26. Soncin F, Mattot V, Lionneton F, et al (2003). VE-statin, an endothelial repressor of smooth muscle cell migration. Embo J, 22, 5700-11.
  27. Sun YX, Cheng W, Han X, et al (2014). In vivo experimental study on the effects of fluid in increasing the efficiency of radiofrequency ablation. Asian Pac J Cancer Prev, 15, 5799-804.
  28. Wu F, Yang LY, Li YF, et al (2009). Novel role for epidermal growth factor-like domain 7 in metastasis of human hepatocellular carcinoma. Hepatology, 50, 1839-50.
  29. Xu C, Lv PH, Huang XE, et al (2014). Safety and efficacy of sequential transcatheter arterial chemoembolization and portal vein embolization prior to major hepatectomy for patients with HCC. Asian Pac J Cancer Prev, 15, 703-6.
  30. Xu D, Perez RE, Ekekezie II, et al (2008). Epidermal growth factor-like domain 7 protects endothelial cells from hyperoxia-induced cell death. Am J Physiol Lung Cell Mol Physiol, 294, 17-23.
  31. Xu HF, Chen L, Liu XD, et al (2014). Targeting EGFL7 expression through RNA interference suppresses renal cell carcinoma growth by inhibiting angiogenesis. Asian Pac J Cancer Prev, 15, 3045-50.

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