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Significance of Suppressor of Cytokine Signaling-3 Expression in Bladder Urothelial Carcinoma in Relation to Proinflammatory Cytokines and Tumor Histopathological Grading

  • Gaballah, Hanaa Hibishy (Medical Biochemistry Department, Faculty of Medicine, Tanta University) ;
  • Shafik, Noha Mohamed (Medical Biochemistry Department, Faculty of Medicine, Tanta University) ;
  • Wasfy, Rania Elsayed (Pathology Department, Faculty of Medicine, Tanta University) ;
  • Farha, Mohamed Osama Abou (Urology Department, Faculty of Medicine, Tanta University)
  • Published : 2015.02.04

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 ($0.36{\pm}0.12$) compared to low grade carcinoma ($1.22{\pm}0.38$) and controls ($4.08{\pm}0.88$), (p<0.001). However, in high grade urothelial carcinoma the urinary levels of IL-6, IL-8, total CK-18($221.33{\pm}22.84pg/ml$, $325.2{\pm}53.6pg/ml$, $466.7{\pm}57.40U/L$ respectively) were significantly higher than their levels in low grade carcinoma ($58.6{\pm}18.6pg/ml$, $58.3{\pm}50.2pg/ml$, $185.5{\pm}60.3U/L$ respectively) and controls ($50.9{\pm}23.0pg/ml$, $7.12{\pm}2.74pg/ml$, $106.7{\pm}47.3U/L$ 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.

Keywords

Suppressor of cytokine signaling-3;interleukins;cytokeratin-18;urothelial carcinoma

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