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NRP‑1 and KDR polymorphisms are associated with survival time in patients with advanced gastric cancer

  • Authors:
    • Yue‑Jian Zhuo
    • Yu Shi
    • Tao Wu
  • View Affiliations / Copyright

    Affiliations: Department of Medical Oncology, The Second Hospital Affiliated to Dalian Medical University, Dalian, Liaoning 116000, P.R. China
    Copyright: © Zhuo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4629-4638
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    Published online on: September 10, 2019
       https://doi.org/10.3892/ol.2019.10842
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Abstract

Neuropilin‑1 (NRP‑1), a member of the NRP‑family, has been reported to be vital for tumor angiogenesis, growth and metastasis. As a co‑receptor of vascular endothelial growth factor (VEGF), NRP‑1 can bind to VEGF and meditate vascular development through the VEGF‑VEGF receptor 2 (VEGFR2) signaling pathway. Furthermore, NRP‑1 is capable of binding with platelet‑derived growth factor (PDGF) to regulate the PDGF‑PDGF receptor (PDGR) signaling pathway in tumor angiogenesis. In the present study, The DNA was obtained from the paraffin‑embedded tissues of patients with advanced gastric cancer (AGC), amplified using PCR and subsequently sequenced to determine the polymorphisms within NRP‑1, VEGFR2 [kinase insert domain receptor (KDR)] and PDGF. The effect of the functional polymorphism of the aforementioned genes on the overall survival (OS) and progression‑free survival (PFS) of 81 patients with advanced gastric cancer was examined. Three single nucleotide polymorphisms (SNPs) of KDR were significantly associated with clinical outcomes. The rs1870377 TT genotype was positively associated with longer OS and PFS times compared with the AA+AT genotype (PFS, P=0.012; OS, P=0.038), the rs7692791 wild‑type TT genotype was positively associated with longer PFS time and the rs2034965 AA+GA genotype was associated with shorter OS time (P=0.034). With regards to the SNPs of NRP‑1, the rs2065364 AA genotype was significantly associated with improved OS and PFS times (PFS, P=0.023; OS, P=0.045). Following multivariate analysis using Cox proportional hazards regression models, patients with the KDR rs7692791 TT genotype experienced a longer PFS time compared with those with the CT genotype (P=0.016), and patients with the NRP‑1 rs2065364 variant‑type AA genotype still experienced a longer PFS time compared with those patients with the AG+GG genotypes (P=0.006). Regarding OS, the results demonstrated that the KDR rs2034965 AG+GG genotypes presented with a significant reduction in OS time (P=0.029), and that the KDR rs1870377 AT+AA genotypes had worse OS times compared with the wild‑type TT genotype (P=0.021). In addition, increased mortality risk and AGC progression were significantly associated with the number of adverse alleles for combinations of NRP‑1 rs2065364 and KDR rs1870377. In conclusion, the data from the present study demonstrated that the selected KDR and NRP‑1 gene polymorphisms may be potential prognostic biomarkers in AGC.
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1 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Wang Y, Li Z, Shan F, Miao R, Xue K, Li Z, Gao C, Chen N, Gao X, Li S and Ji J: Current status of diagnosis and treatment of early gastric cancer in China-Data from China gastrointestinal cancer surgery union. Zhonghua Wei Chang Wai Ke Za Zhi. 21:168–174. 2018.(In Chinese). PubMed/NCBI

3 

Wang FH, Shen L, Li J, Zhou ZW, Liang H, Zhang XT, Tang L, Xin Y, Jin J, Zhang YJ, et al: The Chinese Society of Clinical Oncology (CSCO): Clinical Guidelines for the Diagnosis and Treatment of Gastric Cancer. Cancer Commun (Lond). 39:102019. View Article : Google Scholar : PubMed/NCBI

4 

Van Cutsem E, Sagaert X, Topal B, Haustermans K and Prenen H: Gastric cancer. Lancet. 388:2654–2664. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Chen K, Yang D, Li X, Sun B, Song F, Cao W, Brat DJ, Gao Z, Li H, Liang H, et al: Mutational landscape of gastric adenocarcinoma in Chinese: Implications for prognosis and therapy. Proc Natl Acad Sci USA. 112:1107–1112. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Fujisawa H, Takagi S and Hirata T: Growth-associated expression of a membrane protein, neuropilin, in Xenopus optic nerve fibers. Dev Neurosci. 17:343–349. 1995. View Article : Google Scholar : PubMed/NCBI

7 

Muhl L, Folestad EB, Gladh H, Wang Y, Moessinger C, Jakobsson L and Eriksson U: Neuropilin 1 binds PDGF-D and is a co-receptor in PDGF-D-PDGFRβ signaling. J Cell Sci. 130:1365–1378. 2017. View Article : Google Scholar : PubMed/NCBI

8 

Raimondi C: Neuropilin-1 enforces extracellular matrix signalling via ABL1 to promote angiogenesis. Biochem Soc Trans. 42:1429–1434. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Ferrara N, Gerber HP and LeCouter J: The biology of VEGF and its receptors. Nat Med. 9:669–676. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Karaman S, Leppänen VM and Alitalo K: Vascular endothelial growth factor signaling in development and disease. Development. 145(pii): dev1510192018. View Article : Google Scholar : PubMed/NCBI

11 

Shibuya M and Claesson-Welsh L: Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis. Exp Cell Res. 312:549–560. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Farooqi AA and Siddik ZH: Platelet-derived growth factor (PDGF) signalling in cancer: Rapidly emerging signalling landscape. Cell Biochem Funct. 33:257–265. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Heldin CH, Lennartsson J and Westermark B: Involvement of platelet-derived growth factor ligands and receptors in tumorigenesis. J Intern Med. 283:16–44. 2018. View Article : Google Scholar : PubMed/NCBI

14 

Sa-Nguanraksa D, Kooptiwut S, Chuangsuwanich T, Pongpruttipan T, Malasit P and O-Charoenrat P: Vascular endothelial growth factor polymorphisms affect gene expression and tumor aggressiveness in patients with breast cancer. Mol Med Rep. 9:1044–1048. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Glubb DM, Cerri E, Giese A, Zhang W, Mirza O, Thompson EE, Chen P, Das S, Jassem J, Rzyman W, et al: Novel functional germline variants in the VEGF receptor 2 gene and their effect on gene expression and microvessel density in lung cancer. Clin Cancer Res. 17:5257–5267. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Oken M, Creech R, Tormey D, Horton J, Davis TE, McFadden ET and Carbone PP: Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 5:649–655. 1982. View Article : Google Scholar : PubMed/NCBI

17 

Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL and Trotti A III: AJCC Cancer Staging Manual. 7th. Springer; New York, NY: 2010

18 

National Cancer Institute (NCI), . Common Terminology Criteria for Adverse Events CTCAE). Version 4.03. 2010.

19 

Berardi R, Torniai M, Partelli S, Rubini C, Pagliaretta S, Savini A, Polenta V, Santoni M, Giampieri R, Onorati S, et al: Impact of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) single nucleotide polymorphisms on outcome in gastroenteropancreatic neuroendocrine neoplasms. PLoS One. 13:e01970352018. View Article : Google Scholar : PubMed/NCBI

20 

Zhu X, Wang Y, Xue W, Wang R, Wang L, Zhu ML and Zheng L: The VEGFR-2 protein and the VEGFR-2 rs1870377 A>T genetic polymorphism are prognostic factors for gastric cancer. Cancer Biol Ther. 20:497–504. 2019. View Article : Google Scholar : PubMed/NCBI

21 

Wang W, Ma XP, Shi Z, Zhang P, Ding DL, Huang HX, Saiyin HG, Chen TY, Lu PX, Wang NJ, et al: Epidermal growth factor receptor pathway polymorphisms and the prognosis of hepatocellular carcinoma. Am J Cancer Res. 5:396–410. 2015.PubMed/NCBI

22 

Kim MK, Suh C, Chi HS, Cho HS, Bae YK, Lee KH, Lee GW, Kim IS, Eom HS, Kong SY, et al: VEGFA and VEGFR2 genetic polymorphisms and survival in patients with diffuse large B cell lymphoma. Cancer Sci. 103:497–503. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Kim MJ, Kim SK, Park HJ, Chung DH, Park HK, Lee JS, Kwon KH and Chung JH: PDGFRA promoter polymorphisms are associated with the risk of papillary thyroid cancer. Mol Med Rep. 5:1267–1270. 2012.PubMed/NCBI

24 

Volz NB, Stintzing S, Zhang W, Yang D, Ning Y, Wakatsuki T, El-Khoueiry RE, Li JE, Kardosh A, Loupakis F, et al: Genes involved in pericyte-driven tumor maturation predict treatment benefit of first-line FOLFIRI plus bevacizumab in patients with metastatic colorectal cancer. Pharmacogenomics J. 15:69–76. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Peng Y, Liu YM, Li LC, Wang LL and Wu XL: MicroRNA-338 inhibits growth, invasion and metastasis of gastric cancer by targeting NRP1 expression. PLoS One. 9:e944222014. View Article : Google Scholar : PubMed/NCBI

26 

Lin J, Zhang Y, Wu J, Li L, Chen N, Ni P, Song L and Liu X: Neuropilin 1 (NRP1) is a novel tumor marker in hepatocellular carcinoma. Clin Chim Acta. 485:158–165. 2018. View Article : Google Scholar : PubMed/NCBI

27 

Ding M, Liu L, Hu C, Liu Y, Qiao Y and Jiang X: Expression of VEGFR2 and NRP-1 in non-small cell lung cancer and their clinical significance. Chin J Cancer Res. 26:669–677. 2014.PubMed/NCBI

28 

Wey JS, Gray MJ, Fan F, Belcheva A, McCarty MF, Stoeltzing O, Somcio R, Liu W, Evans DB, Klagsbrun M, et al: Overexpression of neuropilin-1 promotes constitutive MAPK signalling and chemoresistance in pancreatic cancer cells. Br J Cancer. 93:233–241. 2005. View Article : Google Scholar : PubMed/NCBI

29 

Yue B, Ma JF, Yao G, Yang MD, Cheng H and Liu GY: Knockdown of neuropilin-1 suppresses invasion, angiogenesis and increases the chemosensitivity to doxorubicin in osteosarcoma cells-an in vitro study. Eur Rev Med Pharmacol Sci. 18:1735–1741. 2014.PubMed/NCBI

30 

Hansen TF, Sørensen FB, Spindler KL, Olsen DA, Andersen RF, Lindebjerg J, Brandslund I and Jakobsen A: Microvessel density and the association with single nucleotide polymorphisms of the vascular endothelial growth factor receptor 2 in patients with colorectal cancer. Virchows Arch. 456:251–260. 2010. View Article : Google Scholar : PubMed/NCBI

31 

Zhang J, Yang J, Chen Y, Mao Q, Li S, Xiong W, Lin Y, Chen J and Ge J: Genetic variants of VEGF (rs201963 and rs3025039) and KDR (rs7667298, rs2305948, and rs1870377) are associated with glioma risk in a Han Chinese population: A case-control study. Mol Neurobiol. 53:2610–2618. 2016. View Article : Google Scholar : PubMed/NCBI

32 

Andrae J, Gallini R and Betsholtz C: Role of platelet-derived growth factors in physiology and medicine. Genes Dev. 22:1276–1312. 2008. View Article : Google Scholar : PubMed/NCBI

33 

Heldin CH and Westermark B: Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev. 79:1283–1316. 1999. View Article : Google Scholar : PubMed/NCBI

34 

Pietras K, Sjöblom T, Rubin K, Heldin CH and Ostman A: PDGF receptors as cancer drug targets. Cancer Cell. 3:439–443. 2003. View Article : Google Scholar : PubMed/NCBI

35 

Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N, Singer S, Griffith DJ, Haley A, Town A, et al: PDGFRA activating mutations, in gastrointestinal stromal tumors. Science. 299:708–710. 2003. View Article : Google Scholar : PubMed/NCBI

36 

Duan B, Hu J, Liu H, Wang Y, Li H, Liu S, Xie J, Owzar K, Abbruzzese J, Hurwitz H, et al: Genetic variants in the platelet-derived growth factor subunit B gene associated with pancreatic cancer risk. Int J Cancer. 142:1322–1331. 2018. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhuo YJ, Shi Y and Wu T: NRP‑1 and KDR polymorphisms are associated with survival time in patients with advanced gastric cancer. Oncol Lett 18: 4629-4638, 2019.
APA
Zhuo, Y., Shi, Y., & Wu, T. (2019). NRP‑1 and KDR polymorphisms are associated with survival time in patients with advanced gastric cancer. Oncology Letters, 18, 4629-4638. https://doi.org/10.3892/ol.2019.10842
MLA
Zhuo, Y., Shi, Y., Wu, T."NRP‑1 and KDR polymorphisms are associated with survival time in patients with advanced gastric cancer". Oncology Letters 18.5 (2019): 4629-4638.
Chicago
Zhuo, Y., Shi, Y., Wu, T."NRP‑1 and KDR polymorphisms are associated with survival time in patients with advanced gastric cancer". Oncology Letters 18, no. 5 (2019): 4629-4638. https://doi.org/10.3892/ol.2019.10842
Copy and paste a formatted citation
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Spandidos Publications style
Zhuo YJ, Shi Y and Wu T: NRP‑1 and KDR polymorphisms are associated with survival time in patients with advanced gastric cancer. Oncol Lett 18: 4629-4638, 2019.
APA
Zhuo, Y., Shi, Y., & Wu, T. (2019). NRP‑1 and KDR polymorphisms are associated with survival time in patients with advanced gastric cancer. Oncology Letters, 18, 4629-4638. https://doi.org/10.3892/ol.2019.10842
MLA
Zhuo, Y., Shi, Y., Wu, T."NRP‑1 and KDR polymorphisms are associated with survival time in patients with advanced gastric cancer". Oncology Letters 18.5 (2019): 4629-4638.
Chicago
Zhuo, Y., Shi, Y., Wu, T."NRP‑1 and KDR polymorphisms are associated with survival time in patients with advanced gastric cancer". Oncology Letters 18, no. 5 (2019): 4629-4638. https://doi.org/10.3892/ol.2019.10842
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