Differential expression of EphA5 protein in gastric carcinoma and its clinical significance

  • Authors:
    • Wei Zhang
    • Xue Wei
    • Shuwei Guo
    • Jiandong Wang
    • Jing Liu
    • Hai Wang
  • View Affiliations

  • Published online on: March 19, 2019     https://doi.org/10.3892/ol.2019.10167
  • Pages: 5147-5153
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The aim of the present study was to evaluate ephrin type‑A receptor 5 (EphA5) expression and its clinicopathological significance in gastric cancer. Gastric cancer tissues were analyzed by immunohistochemistry. The association between EphA5 expression and clinicopathological parameters, human epidermal growth factor receptor 2 (HER2) status and Ki‑67 proliferation index was statistically analyzed. EphA5 expression was detected in all non‑tumor gastric epithelia but was differentially expressed among gastric cancer samples. EphA5 was negatively expressed in 30/110 (27.3%) and positively expressed in 80/110 (72.3%) samples from patients with gastric cancer. EphA5 expression was significantly associated with Lauren classification (P=0.032), lymph node metastasis (P<0.001), HER2 expression (P=0.020) and Ki‑67 expression (P=0.005). No significant association was determined between EphA5 expression and age, sex, primary location, depth of invasion and Tumor‑Node‑Metastasis stage. The present data indicated that EphA5 is differentially expressed in gastric cancer. EphA5 may therefore be a potential therapeutic target and may have clinical utility as a marker for lymph node metastasis in gastric cancer.

References

1 

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, et al: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial. Lancet. 376:687–697. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Szöllösi J, Balázs M, Feuerstein BG, Benz CC and Waldman FM: ERBB-2 (HER2/neu) gene copy number, p185HER-2 overexpression, and intratumor heterogeneity in human breast cancer. Cancer Res. 55:5400–5407. 1995.PubMed/NCBI

4 

Ramieri MT, Murari R, Botti C, Pica E, Zotti G and Alo PL: Detection of HER2 amplification using the SISH technique in breast, colon, prostate, lung and ovarian carcinoma. Anticancer Res. 30:1287–1292. 2010.PubMed/NCBI

5 

Hofmann M, Stoss O, Shi D, Büttner R, van de Vijver M, Kim W, Ochiai A, Rüschoff J and Henkel T: Assessment of a HER2 scoring system for gastric cancer: Results from a validation study. Histopathology. 52:797–805. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Shitara K, Yatabe Y, Matsuo K, Sugano M, Kondo C, Takahari D, Ura T, Tajika M, Ito S and Muro K: Prognosis of patients with advanced gastric cancer by HER2 status and trastuzumab treatment. Gastric Cancer. 16:261–267. 2013. View Article : Google Scholar : PubMed/NCBI

7 

An E, Ock CY, Kim TY, Lee KH, Han SW, Im SA, Kim TY, Liao WL, Cecchi F, Blackler A, et al: Quantitative proteomic analysis of HER2 expression in the selection of gastric cancer patients for trastuzumab treatment. Ann Oncol. 28:110–115. 2017.PubMed/NCBI

8 

Zhou R, Copeland TD, Kromer LF and Schulz NT: Isolation and characterization of Bsk, a growth factor receptor-like tyrosine kinase associated with the limbic system. J Neurosci Res. 37:129–143. 1994. View Article : Google Scholar : PubMed/NCBI

9 

Symonds AC, King CE, Bartlett CA, Sauvé Y, Lund RD, Beazley LD, Dunlop SA and Rodger J: EphA5 and ephrin-A2 expression during optic nerve regeneration: A ‘two-edged sword’. Eur J Neurosci. 25:744–752. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Washburn CP, Cooper MA and Zhou R: Expression of the tyrosine kinase receptor EphA5 and its ligand ephrin-A5 during mouse spinal cord development. Neurosci Bull. 23:249–255. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Cooper MA, Crockett DP, Nowakowski RS, Gale NW and Zhou R: Distribution of EphA5 receptor protein in the developing and adult mouse nervous system. J Comp Neurol. 514:310–328. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Unified nomenclature for Eph family receptors and their ligands, the ephrins. Eph nomenclature committee. Cell. 90:403–404. 1997. View Article : Google Scholar : PubMed/NCBI

13 

Wang J, Kataoka H, Suzuki M, Sato N, Nakamura R, Tao H, Maruyama K, Isogaki J, Kanaoka S, Ihara M, et al: Downregulation of EphA7 by hypermethylation in colorectal cancer. Oncogene. 24:5637–5647. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Dawson DW, Hong JS, Shen RR, French SW, Troke JJ, Wu YZ, Chen SS, Gui D, Regelson M, Marahrens Y, et al: Global DNA methylation profiling reveals silencing of a secreted form of Epha7 in mouse and human germinal center B-cell lymphomas. Oncogene. 26:4243–4252. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Chen P, Huang Y, Zhang B, Wang Q and Bai P: EphA2 enhances the proliferation and invasion ability of LNCaP prostate cancer cells. Oncol Lett. 8:41–46. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Wang H, Wen J, Wang H, Guo Q, Shi S, Shi Q, Zhou X, Liu Q, Lu G and Wang J: Loss of expression of EphB1 protein in serous carcinoma of ovary associated with metastasis and poor survival. Int J Clin Exp Pathol. 7:313–321. 2013.PubMed/NCBI

17 

Wu R, Wang H, Wang J, Wang P, Huang F, Xie B, Zhao Y, Li S and Zhou J: EphA3, induced by PC-1/PrLZ, contributes to the malignant progression of prostate cancer. Oncol Rep. 32:2657–2665. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Staquicini FI, Qian MD, Salameh A, Dobroff AS, Edwards JK, Cimino DF, Moeller BJ, Kelly P, Nunez MI, Tang X, et al: Receptor tyrosine kinase EphA5 is a functional molecular target in human lung cancer. J Biol Chem. 290:7345–7359. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Fu DY, Wang ZM, Wang BL, Chen L, Yang WT, Shen ZZ, Huang W and Shao ZM: Frequent epigenetic inactivation of the receptor tyrosine kinase EphA5 by promoter methylation in human breast cancer. Hum Pathol. 41:48–58. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Li S, Zhu Y, Ma C, Qiu Z, Zhang X, Kang Z, Wu Z, Wang H, Xu X, Zhang H, et al: Downregulation of EphA5 by promoter methylation in human prostate cancer. BMC Cancer. 15:182015. View Article : Google Scholar : PubMed/NCBI

21 

Chen X, Wang X, Wei X and Wang J: EphA5 protein, a potential marker for distinguishing histological grade and prognosis in ovarian serous carcinoma. J Ovarian Res. 9:832016. View Article : Google Scholar : PubMed/NCBI

22 

Gu S, Feng J, Jin Q, Wang W and Zhang S: Reduced expression of EphA5 is associated with lymph node metastasis, advanced TNM stage, and poor prognosis in colorectal carcinoma. Histol Histopathol. 32:491–497. 2017.PubMed/NCBI

23 

Aaltonen LA and Hamilton SR: Pathology and Genetics of Tumors of the Digestive System. The Tumor-Node-Metastasis (TNM) System of the World Health Organization Classification of Tumors. IARC Press; Lyon: 2000

24 

Laurén P: Pekka Laurén and histological classification of gastric carcinoma. Interview and comment by Timo J Nevalainen. Gut. 62:1230–1231. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Woo CG, Ho WJ, Park YS, Park SR, Ryu MH, Jung HY and Kang YK: A potential pitfall in evaluating HER2 immunohistochemistry for gastric signet ring cell carcinomas. Pathology. 49:38–43. 2017. View Article : Google Scholar : PubMed/NCBI

26 

Cabrero M, Yu Y, Verma A, Yang H, Colla S, Jia Y, Zheng H, Bohannan Z, Ganan-Gomez I, Futreal A, et al: Downregulation of protection of telomeres 1 expression in myelodysplastic syndromes with 7q deletion. Br J Haematol. 173:161–165. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Coccaro N, Zagaria A, Orsini P, Anelli L, Tota G, Casieri P, Impera L, Minervini A, Minervini CF, Cumbo C, et al: RARA and RARG gene downregulation associated with EZH2 mutation in acute promyelocytic-like morphology leukemia. Hum Pathol. 80:82–86. 2018. View Article : Google Scholar : PubMed/NCBI

28 

Shuai F, Wang B and Dong S: MicroRNA-204 inhibits the growth and motility of colorectal cancer cells by downregulation of CXCL8. Oncol Res. 26:1295–1305. 2018. View Article : Google Scholar : PubMed/NCBI

29 

Ulker D, Ersoy YE, Gucin Z, Muslumanoglu M and Buyru N: Downregulation of SCARA5 may contribute to breast cancer via promoter hypermethylation. Gene. 673:102–106. 2018. View Article : Google Scholar : PubMed/NCBI

30 

Ye F, Chen C, Qin J, Liu J and Zheng C: Genetic profiling reveals an alarming rate of cross-contamination among human cell lines used in China. FASEB J. 29:4268–4272. 2015. View Article : Google Scholar : PubMed/NCBI

31 

Chua TC and Merrett ND: Clinicopathologic factors associated with HER2-positive gastric cancer and its impact on survival outcomes-a systematic review. Int J Cancer. 130:2845–2856. 2012. View Article : Google Scholar : PubMed/NCBI

32 

Youngblood VM, Kim LC, Edwards DN, Hwang Y, Santapuram PR, Stirdivant SM, Lu P, Ye F, Brantley-Sieders DM and Chen J: The Ephrin-A1/EPHA2 signaling axis regulates glutamine metabolism in HER2-positive breast cancer. Cancer Res. 76:1825–1836. 2016. View Article : Google Scholar : PubMed/NCBI

33 

Huang G, Chen S, Wang D, Wang R, Lin L, Chen S, Wang L and Huang Q: High Ki67 expression has prognostic value in surgically-resected T3 gastric adenocarcinoma. Clin Lab. 62:141–153. 2016. View Article : Google Scholar : PubMed/NCBI

34 

Yagi T, Inoue N, Yanai A, Murase K, Imamura M, Miyagawa Y, Enomoto Y, Nishimukai A, Takatsuka Y, Hirota S, et al: Prognostic significance of geminin expression levels in Ki67-high subset of estrogen receptor-positive and HER2-negative breast cancers. Breast Cancer. 23:224–230. 2016. View Article : Google Scholar : PubMed/NCBI

35 

Min KW, Kim DH, Son BK, Kim DH, Kim EK, Seo J, Ahn SB, Jo YJ, Park YS and Ha J: A High Ki67/BCL2 index could predict lower disease-free and overall survival in intestinal-type gastric cancer. Eur Surg Res. 58:158–168. 2017. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

June 2019
Volume 17 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Zhang, W., Wei, X., Guo, S., Wang, J., Liu, J., & Wang, H. (2019). Differential expression of EphA5 protein in gastric carcinoma and its clinical significance. Oncology Letters, 17, 5147-5153. https://doi.org/10.3892/ol.2019.10167
MLA
Zhang, W., Wei, X., Guo, S., Wang, J., Liu, J., Wang, H."Differential expression of EphA5 protein in gastric carcinoma and its clinical significance". Oncology Letters 17.6 (2019): 5147-5153.
Chicago
Zhang, W., Wei, X., Guo, S., Wang, J., Liu, J., Wang, H."Differential expression of EphA5 protein in gastric carcinoma and its clinical significance". Oncology Letters 17, no. 6 (2019): 5147-5153. https://doi.org/10.3892/ol.2019.10167