Tumor Biology

, Volume 35, Issue 5, pp 4589–4597 | Cite as

RETRACTED ARTICLE: The prognosis and clinicopathology of CXCR4 in gastric cancer patients: a meta-analysis

  • Mingzhi Han
  • Shunzeng Lv
  • Ya Zhang
  • Ruiyang Yi
  • Bin Huang
  • Hanhui Fu
  • Ruixiang Bian
  • Xingang Li
Research Article


The chemokine receptor 4 (CXCR4) has been widely investigated in diagnosis and prognosis of gastric cancer (GC). However, the impact of CXCR4 on GC patients remains controversial; Here, we conducted a meta-analysis to obtain the precise role of CXCR4 in GC prognosis and clinicopathology. Thirteen published studies with a total of 1,936 patients were included. Original data included the hazard ratio (HR) of overall survival (OS) and odds ratio (OR) in GC patients. We combined HR/OR with 95 % confidence interval (CI) to estimate the hazard. In this study, OS was significantly related to CXCR4 expression, with the HR 2.63 (95 % CI 1.69–4.09; p < 0.0001), and a significant correlation was also revealed between CXCR4 expression and stage (I + II, +) (OR 0.52, 95 % CI 0.32–0.83; p = 0.007), depth of invasion (T1/T2, +) (OR 0.44, 95 % CI 0.27–0.73; p = 0.001), lymph node metastasis (LN, +) (OR 2.30, 95 % CI 1.57–3.36; p < 0.0001), as well as vascular invasion (vas.inv, +) (OR 0.72, 95 % CI 0.53–0.98; p = 0.04). Heterogeneity was observed among the included studies with OS (I 2 = 51 %), stage (I 2 = 78 %), depth of invasion (I 2 = 74 %), lymph node metastasis (I 2 = 64 %), and histology differentiation (I 2 = 79 %). No publication bias was observed. In conclusion, this meta-analysis showed CXCR4 expression indicates poor prognosis in GC patients with advanced stage or deep invasion in GC tissues, which also implied lymph node metastasis and vascular invasion. Thus, CXCR4 could help predict patient prognosis and guide clinical diagnosis and treatment.


CXCR4 Gastric cancer Prognosis Clinicopathology Meta-analysis 



This study was supported by China Scholarship Council, Shandong University Science Technology Innovation Fund (M2011e01, 2013349), and National Natural Science Foundation of China (81172404, 81372720). We were also very grateful to the help of Sandy Lab staff Huihui Kang et al. for their valuable advice.

Conflict of interest



  1. 1.
    Hartgrink HH, Jansen EP, van Grieken NC, van de Velde CJ. Gastric cancer. Lancet. 2009;374:477–90.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Yoshie O, ImaiT NH. Novel lymphocyte-specific CC chemokines and their receptors. J Leukoc Biol. 1997;62:634–44.PubMedGoogle Scholar
  3. 3.
    Müller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature. 2001;410:50–6.CrossRefPubMedGoogle Scholar
  4. 4.
    Taichman RS, Cooper C, Keller ET, Pienta KJ, Taichman NS, McCauley LK. Use of the stromal cell-derived factor-1alpha/CXCR4 pathway in prostate cancer metastasis to bone. Cancer Res. 2002;62:1832–7.PubMedGoogle Scholar
  5. 5.
    Oonakahara K, Matsuyama W, Higashimoto I, Kawabata M, Arimura K, Osame M. Stromal-derived factor-1alpha/CXCL12-CXCR4 axis is involved in the dissemination of NS CLC cells into pleural space. Am J Respir Cell Mol Biol. 2004;30:671–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Kim J, Mori T, Chen SL, Amersi FF, Martinez SR, Kuo C, et al. Chemokine receptor CXCR4 expression in patients with melanoma and colorectal cancer liver metastases and the association with disease outcome. Ann Surg. 2006;244:113–20.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Zhao BC, Wang ZJ, Mao WZ, Ma HC, Han JG, Zhao B, et al. CXCR4/SDF-1 axis is involved in lymph node metastasis of gastric carcinoma. World J Gastroenterol. 2011;17:2389–96.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Lee HJ, Kim SW, Kim HY, Li S, Yun HJ, Song KS, et al. Chemokine receptor CXCR4 expression, function and clinical implications in gastric cancer. Int J Oncol. 2009;34:473–80.PubMedGoogle Scholar
  9. 9.
    Sun TY, Yan W, Zhao YL, Yu PW. CXCR4 expression in gastric cancer and its clinical significance. Chin J Oper Proc Gen Surg. 2011;5:182–7.Google Scholar
  10. 10.
    Tsuboi K, Kodera Y, Nakanishi H, Ito S, Mochizuki Y, Nakayama G, et al. Expression of CXCL12 and CXCR4 in pT3-stage gastric cancer does not correlate with peritoneal metastasis. Oncol Rep. 2008;20:1117–23.PubMedGoogle Scholar
  11. 11.
    Zou P, Zhang ZY, Wu JF. Expressions of chemokine CXCL12 and its receptor CXCR4 in gastric cancer and their significance. J Clin Exp Pathal. 2012;28:265–9.Google Scholar
  12. 12.
    Steels E, Paesmans M, Berghmans T, Branle F, Lemaitre F, Mascaux C, et al. Role of p53 as a prognostic factor for survival in lung cancer: a systematic review of the literature with a meta-analysis. Eur Respir J. 2001;18:705–19.CrossRefPubMedGoogle Scholar
  13. 13.
    Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:16.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998;17:2815–34.CrossRefPubMedGoogle Scholar
  15. 15.
    Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Arigami T, Natsugoe S, Uenosono Y, Yanagita S, Arima H, Hirata M, et al. CCR7 and CXCR4 expression predicts lymph node status including micrometastasis in gastric cancer. Int J Oncol. 2009;35:19–24.CrossRefPubMedGoogle Scholar
  17. 17.
    Lee HJ, Huang SM, Kim HY, Oh YS, Hwang JY, Liang ZL, et al. Evaluation of the combined expression of chemokine SDF-1 α and its receptor CXCR4 as a prognostic marker for gastric cancer. Exp Ther Med. 2011;2:499–504.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Ying J, Xu Q, Zhang G, Liu B, Zhu L. The expression of CXCL12 and CXCR4 in gastric cancer and their correlation to lymph node metastasis. Med Oncol. 2012;29:1716–22.CrossRefPubMedGoogle Scholar
  19. 19.
    Zhu ZQ, Ning ZL, Shao F, Hu B. Liang W (2012) Expression of CXCR4 in gastric cancer and its relationship with patient prognosis. Acad J Sec Mil Med Univ. 2012;33:43–7.CrossRefGoogle Scholar
  20. 20.
    Kwak MK, Hur K, Park DJ, Lee HJ, Lee HS, Kim WH, et al. Expression of chemokine receptors in human gastric cancer. Tumor Biol. 2005;26:65–70.CrossRefGoogle Scholar
  21. 21.
    He H, Wang C, Shen Z, Fang Y, Wang X, Chen W, et al. Upregulated expression of C-X-C chemokine receptor 4 is an independent prognostic predictor for patients with gastric cancer. Plos ONE. 2013;8:e71864.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Ingold B, Simon E, Ungethüm U, Kuban RJ, Müller BM, Lupp A, et al. Vascular CXCR4 expression—a novel antiangiogenic target in gastric cancer? Plos ONE. 2010;5:e10087.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Fulton AM. The chemokine receptors CXCR4 and CXCR3 in cancer. Curr Oncol Rep. 2009;11:125–31.CrossRefPubMedGoogle Scholar
  24. 24.
    Ratajczak MZ, Zuba-Surma E, Kucia M, Reca R, Wojakowski W, Ratajczak J. The pleiotropic effects of the SDF-1-CXCR4 axis in organogenesis, regeneration and tumorigenesis. Leukemia. 2006;20:1915–24.CrossRefPubMedGoogle Scholar
  25. 25.
    Begg CB, Berlin JA. Publication bias: a problem in interpreting medical data. J R Stat Soc A. 1988;81:107–15.Google Scholar
  26. 26.
    Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Mingzhi Han
    • 1
  • Shunzeng Lv
    • 1
    • 2
  • Ya Zhang
    • 3
  • Ruiyang Yi
    • 4
  • Bin Huang
    • 1
  • Hanhui Fu
    • 1
  • Ruixiang Bian
    • 5
  • Xingang Li
    • 1
  1. 1.Department of NeurosurgeryQilu Hospital of Shandong University and Brain Science Research Institute, Shandong UniversityJinanChina
  2. 2.Department of General Surgery, Peking Union Medical College HospitalChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
  3. 3.Department of HematologyShandong Provincial Hospital Affiliated to Shandong UniversityJinanChina
  4. 4.Biological Sciences DivisionUniversity of ChicagoChicagoUSA
  5. 5.Department of Joint SurgeryShandong Provincial Hospital Affiliated to Shandong UniversityJinanChina

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