EphB4 gene polymorphism and protein expression in non-small-cell lung cancer

  • Authors:
    • Ming-Feng Zheng
    • Yong Ji
    • Xiao-Bo Wu
    • Shu-Gao Ye
    • Jing-Yu Chen
  • View Affiliations

  • Published online on: June 6, 2012     https://doi.org/10.3892/mmr.2012.936
  • Pages: 405-408
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Abstract

The objective of this study was to identify new diagnostic, prognostic or therapeutic molecules for non-small- cell lung cancer (NSCLC). We investigated the expression of EphB4, a tyrosine kinase receptor which has been shown to act as a tumor promoter in other cancers. Using immunohistochemistry, we visualized EphB4 expression in 28 samples of NSCLC and 12 samples of adjacent normal tissues. Additionally, we assessed a single-nucleotide polymorphism in EphB4 to determine its effect on protein expression. The correlation of both genotype and protein expression with disease severity was determined. EphB4 was expressed in 53.6% of patients with lung cancer, a significant increase compared to control lung samples (0.0%, P<0.05). Furthermore, EphB4 expression was correlated with differentiation, lymph node metastasis and TNM stage of tumors (P<0.05). Additionally, the polymorphism in EphB4 at rs314310 appeared to correspond to protein expression and disease susceptibility. While the frequencies of CC, CA and AA genotypes were not different between lung cancer patients and healthy controls, the frequencies of C and A alleles were significantly different between these groups (P<0.05). Further analysis showed that the positive rate of EphB4 expression in patients with the AA genotype was significantly higher compared to that in patients with other genotypes (P<0.05). Overexpression of EphB4 plays a role in the occurrence and development of NSCLC, and the polymorphism at rs314310 may predispose individuals to this disease.

References

1 

Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar

2 

Jemal A, Siegel R, Ward E, Murray T, Xu J and Thun MJ: Cancer statistics, 2007. CA Cancer J Clin. 57:43–66. 2007. View Article : Google Scholar

3 

Yang L, Parkin DM, Li LD, Chen YD and Bray F: Estimation and projection of the national profile of cancer mortality in China: 1991–2005. Br J Cancer. 90:2157–2166. 2004.PubMed/NCBI

4 

Murray T, Siegel R, Ward E, et al: Cancer statistics, 2008. CA Cancer J Clin. 58:71–96. 2008. View Article : Google Scholar

5 

Jemal A, Siegel R, Ward E, et al: Cancer statistics, 2006. CA Cancer J Clin. 56:106–130. 2006. View Article : Google Scholar

6 

Pasquale EB: Eph receptor signalling casts a wide net on cell behaviour. Nat Rev Mol Cell Biol. 6:462–475. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Erber R, Eichelsbacher U, Powajbo V, et al: EphB4 controls blood vascular morphogenesis during postnatal angiogenesis. EMBO J. 25:628–641. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Kumar SR, Singh J, Xia G, et al: Receptor tyrosine kinase EphB4 is a survival factor in breast cancer. Am J Pathol. 169:279–293. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Shimosato Y: Histological typing of lung and pleural tumors (3rd edition, 1999): malignant epithelial tumors. Nihon Rinsho. 60:123–131. 2002.PubMed/NCBI

10 

Shen LQ, Wang XC, Zhao J, Di HZ and Zhuang ZX: Association between Eph4 gene polymorphism and non-small cell lung cancer. Chin J Clin Oncol. 31:778–779. 2009.PubMed/NCBI

11 

Lahiri DK and Schnabel B: DNA isolation by a rapid method from human blood samples: effects of MgCl2, EDTA, storage time, and temperature on DNA yield and quality. Biochem Genet. 31:321–328. 1993. View Article : Google Scholar : PubMed/NCBI

12 

Yarden Y and Ullrich A: Growth factor receptor tyrosine kinases. Annu Rev Biochem. 57:443–478. 1988. View Article : Google Scholar : PubMed/NCBI

13 

Himanen JP and Nikolov DB: Eph signaling: a structural view. Trends Neurosci. 26:46–51. 2003. View Article : Google Scholar : PubMed/NCBI

14 

Wang HU, Chen ZF and Anderson DJ: Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell. 93:741–753. 1998. View Article : Google Scholar : PubMed/NCBI

15 

Cheng N, Brantley DM and Chen J: The ephrins and Eph receptors in angiogenesis. Cytokine Growth Factor Rev. 13:75–85. 2002. View Article : Google Scholar : PubMed/NCBI

16 

Stephenson SA, Slomka S, Douglas EL, Hewett PJ and Hardingham JE: Receptor protein tyrosine kinase EphB4 is up-regulated in colon cancer. BMC Mol Biol. 2:15–17. 2001. View Article : Google Scholar : PubMed/NCBI

17 

Takai N, Miyazaki T, Fujisawa K, Nasu K and Miyakawa I: Expression of receptor tyrosine kinase EphB4 and its ligand ephrin-B2 is associated with malignant potential in endometrial cancer. Oncol Rep. 8:567–573. 2001.PubMed/NCBI

18 

Nowotny P, Kwon JM and Goate AM: SNP analysis to dissect human traits. Curr Opin Neurobiol. 11:637–641. 2001. View Article : Google Scholar : PubMed/NCBI

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August 2012
Volume 6 Issue 2

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Copy and paste a formatted citation
APA
Zheng, M., Ji, Y., Wu, X., Ye, S., & Chen, J. (2012). EphB4 gene polymorphism and protein expression in non-small-cell lung cancer. Molecular Medicine Reports, 6, 405-408. https://doi.org/10.3892/mmr.2012.936
MLA
Zheng, M., Ji, Y., Wu, X., Ye, S., Chen, J."EphB4 gene polymorphism and protein expression in non-small-cell lung cancer". Molecular Medicine Reports 6.2 (2012): 405-408.
Chicago
Zheng, M., Ji, Y., Wu, X., Ye, S., Chen, J."EphB4 gene polymorphism and protein expression in non-small-cell lung cancer". Molecular Medicine Reports 6, no. 2 (2012): 405-408. https://doi.org/10.3892/mmr.2012.936