Elevated Plasma Interleukin-35 as a Prognostic Indicator in Localized Clear Cell Renal Cell Carcinoma

Abstract

Purpose: The aim of the study is to investigate the prognostic value of plasma interleukin-35 in the surgical treatment of patients with clear cell renal cell carcinoma (ccRCC). Material and Methods. Plasma IL-35 levels were measured in patients with ccRCC. The cut-off value of IL-35 was determined by the receiver operating characteristic (ROC) analysis and the area under the curve (AUC). The effects of the IL-35 and other clinicopathological characteristics on overall survival (OS) and progression-free survival (PFS) were evaluated using the univariate and multivariate logistic regression analysis.

Result: Sixty-four ccRCC patients admitted to the urology department at the First Affiliated Hospital of Soochow University were selected, of whom 50 were diagnosed with localized ccRCC. Plasma interleukin-35 levels were significantly higher in patients with ccRCC than that in healthy controls. The cut-off value of IL-35 was 99.7 pg/mL. Multivariate analysis selected by univariate analyses demonstrated that the preoperative IL-35 was an independent prognostic factor for 5-year OS (OR: 1.02, 95% CI: 1.01 to 1.04, p < 0.0001) and 5-year PFS (OR: 1.02, 95% CI: 1.00 to 1.03, p=0.011) in all patients with localized ccRCC.

Conclusion: Current results indicate that preoperative IL-35 is an independent prognostic marker for OS and RFS in patients with localized ccRCC after surgery.

Figure 1

Plasma IL-35 level and clinicopathologic characteristics of patients with ccRCC. (a) Plasma IL-35 level among patients with ccRCC and the HC group. ^∗∗∗∗P < 0.0001. (b) Plasma IL-35 level among patients with either advanced ccRCC or localized ccRCC and the HC group. ^∗P < 0.05 and ^∗∗∗∗P < 0.0001. (c) Plasma IL-35 concentration among of patients with different nuclear grades. ^∗P < 0.05. (d) AUC for overall survival in the ROC analysis of plasma IL-35 level, AUC was 88.83%. IL-35, interleukin-35; ccRCC, clear cell renal cell carcinoma; HC; healthy control.

Figure 2

Kaplan–Meier curves of 3-year OS and PFS. (a): Kaplan–Meier curves of 3-year OS according to the IL-35 in localized patients (p=0.029^∗). (b): Kaplan–Meier curves of 3-year PFS according to the IL-35 in localized patients (p=0.0072^∗). Group 1 (low IL-35), group 2 (high IL-35).

Figure 3

Kaplan–Meier curves of 5-year OS and PFS. (a): Kaplan–Meier curves of 5-year OS according to the IL-35 in localized patients (p=0.0082^∗). (b): Kaplan–Meier curves of 5-year PFS according to the IL-35 in localized patients (p=p=0.015^∗). Group 1 (low IL-35), group 2 (high IL-35).

Figure 4

Nomogram for predicting 5-year death risk and progression risk of localized ccRCC patients. (a): Nomogram for predicting 5-year death risk of localized ccRCC patients. (b): Nomogram for predicting 5-year progression risk of localized ccRCC patients.