CXCR7 expression is associated with disease-free and disease-specific survival in cervical cancer patients

Br J Cancer. 2012 Apr 24;106(9):1520-5. doi: 10.1038/bjc.2012.110.


Background: The CXC chemokine receptor (CXCR)7 is involved in tumour development and metastases formation. The aim of the present study was to determine protein expression of CXCR7, its putative co-receptors epidermal growth factor receptor (EGFR) and CXCR4, its predominant ligand CXCL12, their co-dependency and their association with survival in cervical cancer patients.

Methods: CXC chemokine receptor 7, EGFR, CXCR4 and CXCL12 expression were determined immunohistochemically in 103 paraffin-embedded, cervical cancers. Subsequently, associations with patient characteristics were assessed and survival analyses were performed.

Results: CXC chemokine receptor 7 was expressed by 43% of tumour specimens, in a large majority of cases together with either EGFR or CXCR4 (double positive), or both (triple positive). The CXCR7 expression was associated with tumour size (P=0.013), lymph node metastasis (P=0.001) and EGFR expression (P=0.009). CXC chemokine receptor 7 was independently associated with disease-free survival (hazard ratio (HR)=4.3, 95% confidence intervals (CI) 1.7-11.0, P=0.002), and strongly associated with disease-specific survival (HR=3.9, 95% CI 1.5-10.2, P=0.005).

Conclusion: CXC chemokine receptor 7 expression predicts poor disease-free and disease-specific survival in cervical cancer patients, and might be a promising new therapeutic marker. In a large majority of cases, CXCR7 is co-expressed with CXCR4 and/or EGFR, supporting the hypothesis that these receptors assist in CXCR7 signal transduction.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality*
  • Carcinoma, Squamous Cell / pathology
  • Cervix Uteri / metabolism
  • Cervix Uteri / pathology
  • Chemokine CXCL12 / metabolism
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Lymphatic Metastasis
  • Middle Aged
  • Prognosis
  • Receptors, CXCR / metabolism*
  • Receptors, CXCR4 / metabolism
  • Survival Rate
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / mortality*
  • Uterine Cervical Neoplasms / pathology
  • Young Adult


  • ACKR3 protein, human
  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Receptors, CXCR
  • Receptors, CXCR4
  • EGFR protein, human
  • ErbB Receptors