Tumor Biology

, Volume 37, Issue 5, pp 6099–6105 | Cite as

Expression of chemokine receptor CXCR4 is closely correlated with clinical outcome in human nasopharyngeal carcinoma

  • Hengmin Tao
  • Yumei Wei
  • Congan Wang
  • Kun Yang
  • Wei Huang
  • Haitao Liu
  • Baosheng Li
Original Article


The CXC chemokine receptor 4 (CXCR4) has been reported to be involved in the development and progression of nasopharyngeal carcinoma (NPC). However, the role of CXCR4 in clinical outcome and prognosis of NPC patients remains controversial. In the present study, we investigated and reviewed the expression of CXCR4 in NPC tissues and then analyzed the definitive role of CXCR4 in clinical outcome and prognosis. Here, we found that the expression level of CXCR4 was significantly higher in NPC cancer specimens (61/98) than that in paired non-tumor tissues (p < 0.001). Together with our pathological analysis, statistic analysis revealed that CXCR4 expression was indeed closely correlated with UICC stage (p = 0.000), N stage (p = 0.019), and metastasis (p = 0.000). Most importantly, the systematic review combined with our survival and multivariate analysis that revealed high expression of CXCR4 was obviously associated with poor overall survival (OS) (p = 0.000) and progression-free survival (PFS) (p = 0.000) and can act as an independent prognostic factor in NPC patients. In conclusion, this study suggests that CXCR4 is highly activated and expressed in the development of NPC and may be recommended as an indicator in the diagnosis of NPC. Thus, targeting of CXCR4 gene or protein could be used as a potential therapy for NPC.


CXCR4 NPC Survival Progression 



This study was supported by Taishan Scholars Program of Shandong Province, China (ts20120505), and Shandong Provincial Natural Science Foundation (ZR2014YL034). We greatly thank other members of our lab for valuable suggestions and writing.

Compliance with ethical standards

Conflicts of interest



  1. 1.
    Lee AW, Ma BB, Ng WT, et al. Management of nasopharyngeal carcinoma: current practice and future perspective. J Clin Oncol. 2015;33(29):3356–64.CrossRefPubMedGoogle Scholar
  2. 2.
    Janvilisri T. Omics-based identification of biomarkers for nasopharyngeal carcinoma. Dis Markers. 2015;2015:762128.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Kamran SC, Riaz N, Lee N. Nasopharyngeal carcinoma. Surg Oncol Clin N Am. 2015;24(3):547–61.CrossRefPubMedGoogle Scholar
  4. 4.
    Hutajulu SH, Kurnianda J, Tan IB, et al. Therapeutic implications of Epstein-Barr virus infection for the treatment of nasopharyngeal carcinoma. Ther Clin Risk Manag. 2014;10:721–36.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Yao C, Li P, Song H, et al. CXCL12/CXCR4 Axis Upregulates Twist to Induce EMT in Human Glioblastoma. Mol Neurobiol. 2015.Google Scholar
  6. 6.
    Shi P, Fang C, Pang X. Astrocyte elevated gene-1 regulates CCL3/CCR5-induced epithelial-to-mesenchymal transition via Erk1/2 and Akt signaling in cardiac myxoma. Oncol Rep. 2015;34(3):1319–26.PubMedGoogle Scholar
  7. 7.
    Lv S, Sun B, Zhong X, et al. The clinical implications of Chemokine receptor CXCR4 in grade and prognosis of glioma patients: a meta-analysis. Mol Neurobiol. 2015;52(1):555–61.CrossRefPubMedGoogle Scholar
  8. 8.
    Dai C, Lv S, Shi R, et al. Nuclear protein C23 on the cell surface plays an important role in activation of CXCR4 signaling in glioblastoma. Mol Neurobiol. 2015;52(3):1521–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Cheng S, Guo J, Yang Q, et al. Crk-like adapter protein regulates CCL19/CCR7-mediated epithelial-to-mesenchymal transition via ERK signaling pathway in epithelial ovarian carcinomas. Med Oncol. 2015;32(3):47.CrossRefPubMedGoogle Scholar
  10. 10.
    Yang P, Wang G, Huo H, et al. SDF-1/CXCR4 signaling up-regulates survivin to regulate human sacral chondrosarcoma cell cycle and epithelial-mesenchymal transition via ERK and PI3K/AKT pathway. Med Oncol. 2015;32(1):377.CrossRefPubMedGoogle Scholar
  11. 11.
    Wang S, Lu J, Lv L, et al. Expression of Chemokine receptor CXCR4 in nasopharyngeal carcinomas and its clinical significance. Cancer Res Prev and Treat. 2008;35(1):8–10.CrossRefGoogle Scholar
  12. 12.
    Luo H. The role of CXCR4 expression in nasopharyngeal carcinomas. Nanfang Med Univ. 2008;1(1):8.Google Scholar
  13. 13.
    Zheng D, Dong S, Chen J, et al. Expressions and clinical significance of CXCR4 and CCR7 in nasopharyngeal carcinoma. Hainan Med J. 2014;25(11):1567–9.Google Scholar
  14. 14.
    Wang N. Screening of CXCR4 and its expression in nasopharyngeal carcinoma: correlation with metastasis and survival. Zhongshan Univ. 2005;1(1):30–1.Google Scholar
  15. 15.
    Segawa Y, Oda Y, Yamamoto H, et al. Close correlation between CXCR4 and VEGF expression and their prognostic implications in nasopharyngeal carcinoma. Oncol Rep. 2009;21(5):1197–202.PubMedGoogle Scholar
  16. 16.
    Li J, Li H, Liu J, et al. The clinical implications of human telomerase reverse transcriptase expression in grade and prognosis of gliomas: a systematic review and meta-analysis. Mol Neurobiol. 2015.Google Scholar
  17. 17.
    Hu J, Deng X, Bian X, et al. The expression of functional chemokine receptor CXCR4 is associated with the metastatic potential of human nasopharyngeal carcinoma. Clin Cancer Res. 2005;11(13):4658–65.CrossRefPubMedGoogle Scholar
  18. 18.
    Ou DL, Chen CL, Lin SB, et al. Chemokine receptor expression profiles in nasopharyngeal carcinoma and their association with metastasis and radiotherapy. J Pathol. 2006;210(3):363–73.CrossRefPubMedGoogle Scholar
  19. 19.
    Gao Y, Li J, Peng R. Expression of chemokine receptor CXCR4 in nasopharyngeaI carcinoma. Chin J Cancer Prev Treat. 2008;15(8):594–6.Google Scholar
  20. 20.
    Luo HN, Li X, Liu X, et al. Association of CXCR4 and SDF-1 with organ-specific metastasis of nasopharyngeaI carcinoma. Chin J Oncol. 2009;31(4):260–4.Google Scholar
  21. 21.
    Luo DH, Chen QY, Liu H, et al. The independent, unfavorable prognostic factors endothelin A receptor and chemokine receptor 4 have a close relationship in promoting the motility of nasopharyngeal carcinoma cells via the activation of AKT and MAPK pathways. J Transl Med. 2013;11:203.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Liao A, Shi R, Jiang Y, et al. SDF-1/CXCR4 axis regulates cell cycle progression and epithelial-mesenchymal transition via up-regulation of survivin in glioblastoma. Mol Neurobiol. 2014.Google Scholar
  23. 23.
    Richard CL, Blay J. CXCR4 in cancer and its regulation by PPARγ. PPAR Res. 2008;2008:19.CrossRefGoogle Scholar
  24. 24.
    Li X, Huang Y, Xia J, et al. CXCR4 expression in patients with high-risk locally advanced renal cell carcinoma can independently predict increased risk of disease progression and poor overall survival. Asian Pac J Cancer Prev. 2011;12(12):3313–8.PubMedGoogle Scholar
  25. 25.
    Wang L, Wang L, Yang B, et al. Strong expression of chemokine receptor CXCR4 by renal cell carcinoma cells correlates with metastasis. Clin Exp Metastasis. 2009;26(8):1049–54.CrossRefPubMedGoogle Scholar
  26. 26.
    Tachibana K, Hirota S, Iizasa H, et al. The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature. 1998;393(6685):591–4.CrossRefPubMedGoogle Scholar
  27. 27.
    Furusato B, Mohamed A, Uhlén M, Rhim JS. CXCR4 and cancer. Pathol Int. 2010;60(7):497–505.CrossRefPubMedGoogle Scholar
  28. 28.
    Lv B, Yang X, Lv S, et al. CXCR4 signaling induced epithelial-mesenchymal transition by PI3K/AKT and ERK pathways in glioblastoma. Mol Neurobiol. 2015;52(3):1263–8.CrossRefPubMedGoogle Scholar
  29. 29.
    Guo J, Tang B, Sheng XN, et al. Use of CXCR4 expression to predict the efficacy of sorafenib treatment in patients with metastatic renal cell carcinoma. J Clin Oncol. 2011;29(7):359–64.CrossRefGoogle Scholar
  30. 30.
    Ping YF, Yao XH, Chen JH, et al. The anti-cancer compound Nordy inhibits CXCR4-mediated production of IL-8 and VEGF by malignant human glioma cells. J Neurooncol. 2007;84:21–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Cavallaro S. CXCR4/CXCL12 in non-small-cell lung cancer metastasis to the brain. Int J Mol Sci. 2013;14:1713–27.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Gangadhar T, Nandi S, Salgia R. The role of chemokine receptor CXCR4 in lung cancer. Cancer Biol Ther. 2010;9:409–16.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Hengmin Tao
    • 1
    • 2
  • Yumei Wei
    • 1
  • Congan Wang
    • 3
  • Kun Yang
    • 4
  • Wei Huang
    • 1
  • Haitao Liu
    • 5
  • Baosheng Li
    • 1
  1. 1.Department of 6th Radiation OncologyShandong Cancer Hospital and InstituteJinanChina
  2. 2.School of Medicine and Life SciencesUniversity of Jinan, Shandong Academy of Medical SciencesJinanChina
  3. 3.Traditional Chinese Medicine (TCM) Orthopeadics DepartmentAffiliated Hospital of Shandong Academy of Medical SciencesJinanChina
  4. 4.Accounting Office of Pharmacy DepartmentThe Fourth People Hospital of JinanJinanChina
  5. 5.Department of Radiation OncologyPeking University 3rd HospitalBeijingChina

Personalised recommendations