title: Role of co-expression of c-Myc, EZH2 and p27 in prognosis of prostate cancer patients after surgery.
abstract: BACKGROUND
  c-Myc, EZH2 and p27 were defined to modulate the behavior of prostate cancer with pro-tumoral or anti-tumoral effects and had ability in predicting prostate cancer progression, but the research of their co-expression value of prognosis is rarely. This study aimed to investigate the prognostic value of combining tri-marker together in patients with intermediate-risk prostate cancer after surgery.
  
  
  METHODS
  Expression levels of c-Myc, EZH2 and p27 in 129 patients with intermediate-risk prostate cancer were assessed using immunohistochemistry in a semi-quantitative manner. The expression profiles of these three markers were analyzed and investigated for association with biochemical recurrence.
  
  
  RESULTS
  In all, fifty of 129 cases experienced biochemical recurrence during a median follow-up time of 31 months (range, 6 - 60 months). Of these relapse patients, one case without and 10 cases with any single positive marker were observed; 39 cases were detected with any two or all three positive markers (22 cases with any two and 17 cases with all three positive markers). Survival analysis showed that patients with over-expression of c-Myc or EZH2, and lower expression of p27 manifested significantly higher biochemical recurrence rates. Subsequent multivariate analysis revealed that c-Myc, EZH2 and p27 expression statuses showed potential in predicting relapse, respectively. Notably, combining three markers together as a "composite index" (0 or 1, vs. 2 or 3 positive markers) provided powerful prognostic value (HR 6.57, 95% CI 3.02 - 14.31, P < 0.001). There was a significant difference between the patient subgroups with 0 or 1 and those with 2 or 3 positive markers expression statuses, and tri-marker composite index was an independent risk factor for predicting relapse in patients with intermediate-risk prostate cancer after surgery.
  
  
  CONCLUSIONS
  Composite index of c-Myc, EZH2, and p27 can be valued as powerful prognosis parameter for intermediate-risk prostate cancer patients after the surgery, and postoperative adjuvant therapy can be adopted accordingly.
authors.affiliation: Department of Urology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.forename: Ming-kun
authors.initials: MK
authors.lastname: Chen
authors.forename: Jie
authors.initials: J
authors.lastname: Situ
authors.forename: Wen-tao
authors.initials: WT
authors.lastname: Huang
authors.forename: Zu-lan
authors.initials: ZL
authors.lastname: Su
authors.forename: Dan
authors.initials: D
authors.lastname: He
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
mesh_terms: D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000032:analysis*; D000071221:Enhancer of Zeste Homolog 2 Protein; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D009367:Neoplasm Staging; D063151:Polycomb Repressive Complex 2 / Q000032:analysis*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis*
chemical_list: C436291:CDKN1B protein, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D050760:Cyclin-Dependent Kinase Inhibitor p27; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2