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. 2016 Aug 9;7(32):51525-51534.
doi: 10.18632/oncotarget.10492.

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
Affiliations

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

Zewei Wang et al. Oncotarget. .

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.

Keywords: CCL2; CCR2; clear-cell renal cell carcinoma; overall survival; prognostic biomarker.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. CCL2 and CCR2 expression in ccRCC tissues
Representative photograph of CCL2 (A and B) and CCR2 (C and D) immunostaining in tissue microarrays. Original magnificent (200×).
Figure 2
Figure 2. Kaplan Meier analysis of OS (A–C) and RFS (D–F) probabilities based on intratumoral CCL2 and CCR2 expression levels
In (C and F), patients were stratified into 3 groups: group I, both low CCL2 and low CCR2 expression; group II, either high CCL2 or high CCR2 expression; group III, both high CCL2 and high CCR2 expression.
Figure 3
Figure 3. Subgroup analysis to assess prognostic value of CCL2/CCR2 signature in non-metastatic ccRCC patients
Kaplan-Meier analysis of OS in patients classified into Leibovich low-risk group (A), Leibovich intermediate-risk group (B), and Leibovich high-risk group (C). Kaplan-Meier analysis of RFS in patients classified into Leibovich low-risk group (D), Leibovich intermediate-risk group (E), and Leibovich high-risk group (F).
Figure 4
Figure 4. Nomogram and calibration plots for the prediction of outcome in patients with non-metastatic ccRCC
Nomogram to predict OS and RFS at 5 and 10 years after nephrectomy (A and C), the calibration plots for predicting OS and RFS at 10 years (B and D).
See this image and copyright information in PMC

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