Significance of suppressor of cytokine signaling-3 expression in bladder urothelial carcinoma in relation to proinflammatory cytokines and tumor histopathological grading

Abstract

Background: Bladder cancer is among the five most common malignancies worldwide. Altered expression of suppressor of cytokine signaling -3 (SOCS-3) has been implicated in various types of human cancers; however, its role in bladder cancer is not well established. Aim: The present study was undertaken to investigate the mRNA expression of SOCS-3 in normal and cancerous bladder tissue and to explore its correlation with urinary levels of some proinflammatory cytokines, cytokeratin-18 (CK -18) and with tumor histopathological grading, in order to evaluate their role as potential diagnostic markers. Materials and Methods: SOCS3 mRNA expression levels were evaluated using quantitative real time PCR. Urinary levels of interleukins 6 and 8 were estimated by enzyme linked immunosorbent assay (ELISA). Cytokeratin-18 expression was analyzed by immuunohistochemistry then validated by ELISA. Results: SOC3 m RNA expression levels were significantly lower in high grade urothelial carcinoma (0.36±0.12) compared to low grade carcinoma (1.22±0.38) and controls (4.08±0.88), (p<0.001). However, in high grade urothelial carcinoma the urinary levels of IL-6, IL-8, total CK-18(221.33±22.84 pg/ml, 325.2±53.6 pg/ ml, 466.7±57.40 U/L respectively) were significantly higher than their levels in low grade carcinoma (58.6±18.6 pg/ ml, 58.3±50.2 pg/ml, 185.5±60.3 U/L respectively) and controls (50.9±23.0 pg/ml, 7.12±2.74 pg/ml, 106.7±47.3U/L respectively), (p<0.001). Conclusions: Advanced grade of urothelial bladder carcinoma is significantly associated with lowered mRNA expression of SOC3 as well as elevated urinary levels of proinflammatory cytokines and CK-18. Furthermore, our results suggested that urinary IL-8, IL-6 and CK-18 may benefit as noninvasive biomarkers for early detection as well as histopathological subtyping of urothelial carcinoma.