title: Prognostic value of interleukin-6 and interleukin-6 receptor in organ-confined clear-cell renal cell carcinoma: a 5-year conditional cancer-specific survival analysis.
abstract: BACKGROUND
  Interleukin-6 (IL-6) is the major cytokine that induces transcriptional acute and chronic inflammation responses, and was recently incorporated as a recurrence prognostication signature for localised clear-cell renal cell carcinoma (ccRCC). As the prognostic efficacy of initial risk factors may ebb during long-term practice, we aim to report conditional cancer-specific survival (CCSS) of RCC patients and evaluate the impact of IL-6 as well as its receptor (IL-6R) to offer more relevant prognostic information accounting for elapsing time.
  
  
  METHODS
  We enrolled 180 histologically proven localised ccRCC patients who underwent nephrectomy between 2001 and 2004 with available pathologic information. Five-year CCSS was determined and stratified by future prognostic factors. Constant Cox regression analysis and Harrell's concordance index were used to indicate the predictive accuracy of established models.
  
  
  RESULTS
  The 5-year CCSS of organ-confined ccRCC patients with both IL-6- and IL-6R-positive expression was 52% at year 2 after surgery, which was close to locally advanced patients (48%, P=0.564) and was significantly poorer than organ-confined patients with IL-6- or IL-6R-negative expression (89%, P<0.001). Multivariate analyses proved IL-6 and IL-6R as independent predictors after adjusting for demographic factors. Concordance index of pT-IL-6-IL-6R risk stratification was markedly higher compared with the stage, size, grade and necrosis prognostic model (0.724 vs 0.669, P=0.002) or UCLA Integrated Staging System (0.724 vs 0.642, P=0.007) in organ-confined ccRCC population during the first 5 years.
  
  
  CONCLUSIONS
  Combined IL-6 and IL-6R coexpression emerges as an independent early-stage immunologic prognostic factor for organ-confined ccRCC patients.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Urology, Shanghai Cancer Center, Shanghai Medical College, Fudan University, Mailbox 226, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: An
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
authors.forename: Hangcheng
authors.initials: H
authors.lastname: Fu
authors.affiliation: Department of Urology, Shanghai Cancer Center, Shanghai Medical College, Fudan University, Mailbox 226, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Le
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Weijuan
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Xu
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000737:chemistry* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis*; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D019947:Receptors, Interleukin-6 / Q000032:analysis*; D018570:Risk Assessment; D015996:Survival Rate; D013997:Time Factors
chemical_list: D015850:Interleukin-6; D019947:Receptors, Interleukin-6