title: Ubiquitin D is an independent prognostic marker for survival in stage IIB-IIC colon cancer patients treated with 5-fluoruracil-based adjuvant chemotherapy.
abstract: BACKGROUND
  Postoperative 5-fluoruracil (5-FU)-based adjuvant chemotherapy is recommended for stage II colon cancer patients with high conventional risk factors; however, some of these patients still experience tumor recurrence. Identifying novel biomarkers to distinguish the risk of tumor recurrence after surgery is vital for improving their prognoses. We previously showed that ubiquitin D (UBD) can predict the prognosis of colon cancer; however, there are limited data on whether UBD is an independent prognostic factor for stage II patients treated with 5-FU-based adjuvant chemotherapy.
  
  
  METHODS
  Quantitative real-time PCR and Western blot analyses were used to examine UBD expression in randomly selected stage II patients' tumor tissues. UBD expression and p65 distribution were assessed using immunohistochemistry in paraffin-embedded specimens from the 101 tumor recurrence patients and 178 nonrelapse patients who received postoperative 5-FU-based adjuvant chemotherapy.
  
  
  RESULTS
  UBD expression, both at transcriptional and posttranscriptional levels, was higher in relapse tumors (P < 0.001). Immunohistochemistry staining of UBD and p65 showed significant differences between the two groups (P < 0.001). Patients with tumor tissues that UBD-positive expression alone or in combination with p65 nuclei translocation recurred early had a significantly shorter survival time (P < 0.001), especially in stage IIB-IIC patients. UBD-positive expression accompanied with p65 nuclei translocation was a significant independent predictive high risk factor for overall survival (HR 8.76; 95% CI, 5.35-14.27; P = 0.004) and disease-free survival (HR 5.70; 95% CI, 1.43-11.55; P = 0.016).
  
  
  CONCLUSIONS
  UBD may help to identify recurrent risk in stage IIB-IIC colon cancer patients and further predict which patients benefit from postoperative 5-FU-based adjuvant chemotherapy.
authors.affiliation: Department of General Surgery, First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Senlin
authors.initials: S
authors.lastname: Zhao
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Huamei
authors.initials: H
authors.lastname: Tang
authors.forename: Feifei
authors.initials: F
authors.lastname: Cui
authors.forename: Chenchen
authors.initials: C
authors.lastname: Liu
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.forename: Huijun
authors.initials: H
authors.lastname: Lu
authors.forename: Yingming
authors.initials: Y
authors.lastname: Xue
authors.forename: Weiliang
authors.initials: W
authors.lastname: Jiang
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Peng
authors.forename: Dongwang
authors.initials: D
authors.lastname: Yan
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D003082:Colectomy; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D014452:Ubiquitins / Q000032:analysis* / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C109184:UBD protein, human; D014452:Ubiquitins; D005472:Fluorouracil
keywords: adjuvant chemotherapy; prognosis; stage II colon cancer; ubiquitin D