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.

Angiogenic, inflammatory and immunologic markers in predicting response to sunitinib in metastatic renal cell carcinoma

“…The reasons for CRP elevations in cancer patients are not clearly understood; however, several possible mechanisms have been suggested to explain the association between cancer and increased CRP levels . One possible explanation might be that tumor growth causes inflammation around the tumor, thereby elevating the level of CRP . Alternatively, chronic inflammation, for which CRP is useful in monitoring, may cause cancer progression.…”

“…(15) One possible explanation might be that tumor growth causes inflammation around the tumor, thereby elevating the level of CRP. (16,17) Alternatively, chronic inflammation, for which CRP is useful in monitoring, may cause cancer progression. In addition, inflammatory cytokines may facilitate cancer progression by promoting cancer cell growth and proliferation.…”

PAMOGK: A Pathway Graph Kernel based Multi-Omics Clustering Approach for Discovering Cancer Patient Subgroups

“…[19] reports that IL6 and its related signaling pathways are key factors of development of KIRC and its spread. Others [32,37,11] also report the prognostic value of IL6 for KIRC. The second most influential pathway is the regulation of p38-alpha and p38-beta pathway.…”

Glasgow prognostic score is superior to other inflammation-based scores in predicting survival of diffuse large B-cell lymphoma

“…Harrell's concordance index, an extension of the area under the receiver operative curve (AUC) to survival data, was used to assess the predictive accuracy of different biomarkers [12,13]. P ≤ 0.05(twosided) were considered to be significant.…”