title: NDRG2 is involved in the oncogenic properties of renal cell carcinoma and its loss is a novel independent poor prognostic factor after nephrectomy.
abstract: BACKGROUND
  Although NDRG2 is a candidate tumor suppressor, its exact role in renal cell carcinoma (RCC) is not fully understood. We investigated the functional role of NDRG2 and its clinical relevance in RCC tumorigenesis.
  
  
  METHODS
  NDRG2 expression and its clinical implications in clear cell RCC were evaluated. Biological function was assessed by a proliferation assay, anchorage-independent growth assay, and wound healing and transwell migration assays in RCC cell lines overexpressing NDRG2 coupled with an investigation of the effects of NDRG2 expression on the epithelial-mesenchymal transition (EMT).
  
  
  RESULTS
  NDRG2 was differentially expressed in patients with RCC. A loss of NDRG2 was significantly associated with a higher proportion of tumors >10 cm and a high nuclear grade. Furthermore, multivariate analyses indicated that a loss of NDRG2 was an independent poor prognostic factor for patient survival (recurrence-free survival, hazard ratio 7.901; disease-specific survival, hazard ratio 15.395; overall survival, hazard ratio 11.339; P < 0.001 for all parameters). NDRG2 expression inhibited the anchorage-independent growth and migration of RCC cells. NDRG2 expression also modulated the expression of EMT-related genes such as Snail, Slug, and SIP1, and it decreased EMT signaling in RCC cells. Finally, NDRG2 recovered E-cadherin expression in E-cadherin-negative RCC cells.
  
  
  CONCLUSIONS
  These results indicate that a lack of NDRG2 is associated with oncogenic properties through the loss of its role as a tumor suppressor, and that NDRG2 is an independent poor prognostic factor predicting survival in clear cell RCC, suggesting that it can serve as a novel prognostic biomarker.
authors.affiliation: Department of Pathology, Cancer Research Institute, and Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
authors.forename: Zhe Long
authors.initials: ZL
authors.lastname: Liang
authors.forename: Kyeongah
authors.initials: K
authors.lastname: Kang
authors.forename: Sukjoon
authors.initials: S
authors.lastname: Yoon
authors.forename: Song Mei
authors.initials: SM
authors.lastname: Huang
authors.forename: Jae Sung
authors.initials: JS
authors.lastname: Lim
authors.forename: Jin Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Lim
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D000368:Aged; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D009367:Neoplasm Staging; D009392:Nephrectomy / Q000401:mortality*; D011183:Postoperative Complications; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015996:Survival Rate; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing
chemical_list: C466228:NDRG2 protein, human; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins