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

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.