CCL2/CCR2 axis is associated with postoperative survival and recurrence of patients with non-metastatic clear-cell renal cell carcinoma

// Zewei Wang 1, * , Huyang Xie 2, 3, * , Lin Zhou 4, * , Zheng Liu 1 , Hangcheng Fu 1 , Yu Zhu 2, 3 , Le Xu 5 , Jiejie Xu 1 1 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China 2 Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China 3 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China 4 Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China 5 Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China * These authors contributed equally to this work Correspondence to: Le Xu, email: XL11887@rjh.com.cn Jiejie Xu, email: jjxufdu@fudan.edu.cn Keywords: clear-cell renal cell carcinoma, CCL2, CCR2, prognostic biomarker, overall survival Received: March 27, 2016      Accepted: June 30, 2016      Published: July 08, 2016 ABSTRACT Purpose: Chemokine (C-Cmotif) ligand 2 (CCL2) is a major chemokine that recruit monocytes and macrophages to the sites of inflammation. Recent researches have clarified that overexpression of CCL2 is associated with unfavorable prognosis in various cancer types. In this study, we aim to determine the prognostic value of CCL2 expression as well as its receptor C-C motif receptor type 2 (CCR2) in patients with non-metastatic clear cell renal cell carcinoma (ccRCC) after surgery. Results: Both high CCL2 and CCR2 expression were remarkably correlated with shortened survival time ( P < 0.001 and P < 0.001, respectively) and increased risk of recurrence ( P = 0.001 and P = 0.003, respectively). The combination of CCL2 and CCR2 expression (CCL2/CCR2 signature) could offer a better prognostic stratification. Furthermore, multivariate analyses identified CCL2/CCR2 signature as an independent risk factor for overall survival (OS) and recurrence-free survival (RFS) ( P = 0.007 and P = 0.043, respectively). The incorporation of CCL2/CCR2 signature would refine individual risk stratification and predictive accuracy of the well-established models. Materials and Methods: We retrospectively examined the intratumoral expression of CCL2 and CCR2 by immunohistochemical staining in 268 histologically proven non-metastatic ccRCC patients receiving surgery in a single institution between 2001 and 2004. Kaplan-Meier analysis and Cox regression were applied to determine the prognostic value of CCL2 and CCR2 expression. Concordance index was calculated to compare predictive accuracy of the established models. Conclusions: Combined CCL2 and CCR2 expression emerges as an independent prognostic factor for non-metastatic ccRCC patients after surgical treatment.