title: High expression of chemokine CCL2 is associated with recurrence after surgery in clear-cell renal cell carcinoma.
abstract: OBJECTIVE
  Chemokine (C-C motif) ligand 2 (CCL2) is known to recruit monocytes and macrophages to sites of inflammation. Recent studies suggest CCL2 is overexpressed in multiple cancer types and may play a role in the tumor progression. The aim of this study was to assess the association between CCL2 expression and the risk of recurrence after surgery in patients with clear-cell renal cell carcinoma (ccRCC).
  
  
  METHODS
  This study included 268 ccRCC patients who underwent nephrectomy at a single institute between 2001 and 2004. Clinicopathologic variables and recurrence-free survival (RFS) were recorded. CCL2 expression levels were evaluated by immunohistochemical staining in tumor tissues. Kaplan-Meier method was applied to compare survival curves. Cox regression models were fitted to analyze the effect of prognostic factors on recurrence-free survival (RFS). Harrell's concordance index was calculated to assess predictive accuracy.
  
  
  RESULTS
  High CCL2 expression was associated with a greater risk of recurrence in ccRCC patients (P<0.001). Multivariate analysis confirmed that CCL2 expression was an independent prognostic factor for RFS (P = 0.045). The predictive accuracy of the Leibovich prognostic score was improved when CCL2 expression was added (0.76 vs. 0.71, P<0.001). Notably, the improvement in prediction was more pronounced in patients with low-risk disease. A nomogram integrating CCL2 expression and pathologic factors was then constructed, which predicted 5- and 10-year RFS well for ccRCC patients.
  
  
  CONCLUSIONS
  High chemokine CCL2 expression is an independent predictor of recurrence in ccRCC patients. Evaluation of CCL2 could help guide postsurgical management for ccRCC patients.
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Yuanfeng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Changwen
authors.initials: C
authors.lastname: Zhai
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Tianming
authors.initials: T
authors.lastname: Shi
authors.affiliation: Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Tan
authors.affiliation: Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: XL11887@rjh.com.cn.
authors.forename: Le
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China. Electronic address: jjxufdu@fudan.edu.cn.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000601:surgery; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009392:Nephrectomy / Q000379:methods; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D018932:Chemokine CCL2
keywords: CCL2; Clear-cell renal cell carcinoma; Nomogram; Prognostic biomarker; Recurrence-free survival