title: 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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors: Medical Biochemistry Department, Faculty of Medicine, Tanta University, Egypt E-mail : hanaahibishy@hotmail.com.
authors: Hanaa Hibishy
authors: HH
authors: Gaballah
authors: Noha Mohamed
authors: NM
authors: Shafik
authors: Rania Elsayed
authors: RE
authors: Wasfy
authors: Mohamed Osama
authors: MO
authors: Abou Farha
mesh_terms: D014408:Biomarkers, Tumor / Q000652:urine; D002295:Carcinoma, Transitional Cell / Q000473:pathology*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000652:urine*; D016209:Interleukin-8 / Q000652:urine*; D053538:Keratin-18 / Q000652:urine; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D012372:ROC Curve; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000473:pathology*; D019459:Urothelium / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C508606:CXCL8 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D053538:Keratin-18; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins