title: URG4 overexpression is correlated with cervical cancer progression and poor prognosis in patients with early-stage cervical cancer.
abstract: BACKGROUND
  Upregulator of cell proliferation 4 (URG4) has been implicated in the oncogenesis of certain cancers. However, the correlation between URG4 expression and clinicopathological significance in human cancer remains unclear. Therefore, this study investigated its expression and clinicopathological significance in cervical cancer patients.
  
  
  METHODS
  URG4 expression was examined using quantitative PCR (qPCR) and western blotting in normal cervical epithelial cells, cervical cancer cells, and eight matched pairs of cervical cancer tissues and adjacent noncancerous tissues from the same patient. In addition, immunohistochemistry (IHC) was used to examine URG4 expression in paraffin-embedded tissues from 167 cervical cancer patients (FIGO stages Ib1-IIa2). Statistical analyses were performed to evaluate associations between URG4 expression and prognostic and diagnostic factors.
  
  
  RESULTS
  URG4 was significantly upregulated in the cervical cancer cell lines and tissues compared with the normal cells and adjacent noncancerous cervical tissues. IHC revealed high URG4 expression in 59 out of the 167 (35.13%) cervical cancer specimens. Its expression was significantly correlated with clinical stage (P < 0.0001), tumour size (P = 0.012), T classification (P = 0.023), lymph node metastasis (P = 0.001) and vaginal involvement (P = 0.002). Patients with high URG4 expression, particularly those who received concurrent chemotherapy and radiotherapy (P < 0.0001), showed a shorter overall survival (OS) and disease-free survival (DFS) compared to those with the low expression of this protein. Multivariate analysis revealed that URG4 expression is an independent prognostic factor for cervical cancer patients.
  
  
  CONCLUSIONS
  Our results demonstrated that elevated URG4 protein expression is associated with a poor outcome in patients with early-stage cervical cancer. URG4 may be a novel prognostic marker and therapeutic target for the treatment of cervical cancer.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.forename: Longjuan
authors.initials: L
authors.lastname: Zhang
authors.forename: Teng
authors.initials: T
authors.lastname: Hou
authors.forename: Shu
authors.initials: S
authors.lastname: Wu
authors.forename: Qidan
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou 510060, PR China. lb.song1@gmail.com.
authors.forename: Libing
authors.initials: L
authors.lastname: Song
authors.forename: Jihong
authors.initials: J
authors.lastname: Liu
mesh_terms: D000328:Adult; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D047368:Tumor Burden; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D055815:Young Adult
chemical_list: D009363:Neoplasm Proteins; C470990:URGCP protein, human