Low CCL-21 expression associates with unfavorable postoperative prognosis of patients with metastatic renal cell carcinoma

Oncotarget. 2017 Apr 11;8(15):25650-25659. doi: 10.18632/oncotarget.12827.

Abstract

Background: Chemokine (C-C motif) ligand 21 (CCL21), a ligand of the chemokine (C-C motif) receptor 7, has recently been identified as an immuno-based anti-cancer molecule for its dendritic cells and T lymphocytes chemoattractant function. The aim of this study was to investigate prognostic values of CCL21 expression in metastatic renal cell carcinoma patients treated with targeted therapy.

Methods: This study included 111 patients with metastatic renal cell carcinoma receiving targeted therapy. CCL21 expression was analyzed by immunohistochemistry on tissue microarrays. Prognostic value of tumoral CCL21 expression and patients' clinical outcomes were evaluated.

Results: Kaplan-Meier method showed that low CCL21 expression was associated with shorter patient overall survival and progression-free survival (overall survival, P = 0.005; progression-free survival, P = 0.044). Further stratified analysis showed that low CCL21 expression was significantly associated with shorter overall survival in clear cell renal cell carcinoma patients (P = 0.017) and patients treated with sorafenib (P = 0.009). Low CCL21 expression was also an adverse independent risk factor for overall survival (hazard ratio, 2.106; 95% CI, 1.286-3.450; P = 0.003) and progression-free survival (hazard ratio 1.617; 95%CI 1.060-2.465; P = 0.026) in multivariate analyses. CCL21 expression was significantly associated with treatment best response to targeted therapy (P = 0.009). This molecule could also be combined with Heng risk model to increase its overall survival predictive accuracy.

Conclusion: Low CCL21 expression was a potential independent adverse prognostic biomarker for overall survival and progression-free survival for metastatic renal cell carcinoma patients treated with targeted therapy.

Keywords: CCL-21; metastatic renal cell carcinoma; overall survival; prognostic factor; progression-free survival.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor
  • Carcinoma, Renal Cell / diagnosis
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / mortality*
  • Carcinoma, Renal Cell / surgery
  • Chemokine CCL21 / genetics*
  • Chemokine CCL21 / metabolism
  • Combined Modality Therapy
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / diagnosis
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / mortality*
  • Kidney Neoplasms / surgery
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Postoperative Period
  • Prognosis
  • Proportional Hazards Models
  • ROC Curve
  • Risk Factors
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Chemokine CCL21