title: DHCR24 is an independent predictor of progression in patients with non-muscle-invasive urothelial carcinoma, and its functional role is involved in the aggressive properties of urothelial carcinoma cells.
abstract: OBJECTIVE
  The DHCR24 gene that encodes 3b-hydroxysterol Δ24-reductase, an oxidoreductase involved in cholesterol biosynthesis, has been identified as a progression-related gene based on the quantitative real-time PCR (qPCR) gene signature. Here, the functional role of DHCR24 and its clinical relevance in non-muscle-invasive urothelial carcinoma (NMIUC) were investigated.
  
  
  METHODS
  Primary NMIUC tissue specimens (n = 162) were analyzed by qPCR. Immunohistochemical staining was also performed on 63 subsets of NMIUC tissues. The present study was also undertaken in order to verify the effect of DHCR24 on human urothelial carcinoma cells.
  
  
  RESULTS
  The mRNA expression levels of DHCR24 were significantly higher for patients in with higher grades of tumors than for those with lower grades of tumors (P = 0.003). Kaplan-Meier estimates revealed significant differences in the time to progression between low- and high-mRNA expression groups (log-rank test, P < 0.001). Multivariate Cox regression analysis revealed that the level of DHCR24 expression is an independent predictor of progression (hazard ratio, 5.464; 95 % confidence interval, 1.746-17.099; P = 0.004). The results of immunohistochemical staining were generally concordant with mRNA expression levels. Enforced expression of DHCR24 caused proliferation, adhesion, and migration, while DHCR24 loss resulted in slower proliferation and a reduction in cell viabilities compared with control cells.
  
  
  CONCLUSIONS
  DHCR24 was found to be closely associated with progression among patients with NMIUC and showed aggressive properties in human UC cells.
authors.affiliation: Section of Urologic Oncology and Dean and Betty Gallo Prostate Cancer Center, Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
authors.forename: Geun Taek
authors.initials: GT
authors.lastname: Lee
authors.forename: Yun-Sok
authors.initials: YS
authors.lastname: Ha
authors.forename: Yeon Suk
authors.initials: YS
authors.lastname: Jung
authors.forename: Sung-Kwon
authors.initials: SK
authors.lastname: Moon
authors.forename: Ho Won
authors.initials: HW
authors.lastname: Kang
authors.forename: Ok-Jun
authors.initials: OJ
authors.lastname: Lee
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Joung
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Seok-Joong
authors.initials: SJ
authors.lastname: Yun
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.forename: Isaac Yi
authors.initials: IY
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000736:Androstenes / Q000494:pharmacology; D002277:Carcinoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics*; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult
chemical_list: D000736:Androstenes; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C006261:3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one; D044925:Oxidoreductases Acting on CH-CH Group Donors; C499055:DHCR24 protein, human