title: Clinical significance of tumor-derived IL-1β and IL-18 in localized renal cell carcinoma: Associations with recurrence and survival.
abstract: OBJECTIVE
  Interleukin-1β (IL-1β) and IL-18 are products of activated inflammasomes that play central roles in innate immunity and inflammation. This study was aimed to determine the effect of tumor-derived IL-1β and IL-18 on recurrence and survival of patients with localized clear cell renal cell carcinoma (ccRCC) following surgery.
  
  
  METHODS
  We retrospectively enrolled 267 patients with localized ccRCC undergoing nephrectomy at a single center. Clinicopathologic features, recurrence-free survival (RFS), and overall survival (OS) were recorded. IL-1β and IL-18 levels were assessed by immunohistochemistry in tumor tissues. The Kaplan-Meier method was used to compare survival curves. Cox regression models were used to analyze the effect of prognostic factors on RFS and OS. Concordance index was calculated to assess predictive accuracy.
  
  
  RESULTS
  Both high IL-1β and high IL-18 levels were associated with increased risk of recurrence (P<0.001 and P<0.001, respectively) and reduced survival (P<0.001 and P = 0.001, respectively). The combination of IL-1β and IL-18 expression (IL-1β/IL-18 signature) could further refine prognostic stratification. Multivariate analyses confirmed that IL-1β/IL-18 signature was an independent prognostic factor for RFS and OS (P = 0.005 and P = 0.044, respectively). The predictive accuracy of well-established prognostic models improved when the IL-1β/IL-18 signature was added. Notably, the improvement in prediction was mainly observed in patients with low-risk disease.
  
  
  CONCLUSIONS
  The combined high expression of IL-1β and IL-18 is an independent predictor for poor prognosis in patients with localized ccRCC, and the prognostic value is more pronounced in patients with low-risk disease.
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Le
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Urology, Ninth People׳s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: An
authors.affiliation: Key Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Yidong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: zongminglin@gmail.com.
authors.forename: Zongming
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: wang.guomin@zs-hospital.sh.cn.
authors.forename: Guomin
authors.initials: G
authors.lastname: Wang
authors.affiliation: Key Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: jjxufdu@fudan.edu.cn.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Xu
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D002681:China / Q000453:epidemiology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D020382:Interleukin-18; D053583:Interleukin-1beta
keywords: Clear cell renal cell carcinoma; IL-18; IL-1β; Overall survival; Prognostic biomarker; Recurrence-free survival