Urinary IL-6 and IL-8 as predictive markers in bladder urothelial carcinoma: A pilot study.

Abstract

Cytokines are known to be a key a factor in numerous malignancies and to exert an important regulatory role in the tumor microenvironment. Interest has grown in understanding how cytokines modulate the tumor microenvironment and which cytokines may serve as markers of the tumor process; however, a complete picture of the cytokine landscape in bladder cancer remains unclear. Fresh urine specimens with sufficient volume were collected at random intervals. The urine concentrations of IL-8 (CXCL8), CCL18, and CXCL9 were determined using the standard commercially available enzyme immunoassay. The urine concentrations of IL-6 were determined using the high sensitivity enzyme immunoassay kit. Urinary cytokine concentrations were normalized with urinary creatinine concentrations. Significantly elevated concentrations of IL-6 and IL-8 were detected in the urine from patients with urothelial carcinoma on follow-up compared to patients with benign follow-up. The presence of both IL-6 and IL-8 in the urine samples from the high grade urothelial carcinoma (HGUC) cohort revealed a clear discrimination when compared to samples from patients with benign follow-up. The presence of the combination of both IL-6 and IL-8 had a sensitivity of 90.0% and a specificity of 81.25%. Similar data were obtained when receiver operating characteristic analysis was performed on both IL-6 and IL-8 concentrations in the urine from patients with HGUC vs. the hematuria cohort. The presence of IL-6 and IL-8 in urine specimens may have predictive value for urothelial carcinoma. However, a large longitudinal study is required to statistically eliminate confounding factors and support this theory.