title: The prognostic role of EZH2 expression in rectal cancer patients treated with neoadjuvant chemoradiotherapy.
abstract: BACKGROUND
  Neoadjuvant chemoradiotherapy (nCRT) combined with surgery has been implemented as a standard treatment strategy in locally advanced rectal cancer (LARC). However, there is a wide spectrum of response to nCRT. The aim of this study was to determine whether enhancer of zeste homologue 2 (EZH2 ) expression could predict response to nCRT and outcomes for patients in LARC.
  
  
  METHODS
  The study examined the EZH2 expression in 112 biopsies by immohistochemistry. The associations between EZH2 and clinical characters were analyzed.
  
  
  RESULTS
  EZH2 expression in biopsy tissue was significantly related to increased tumor cell proliferation, as assessed by Ki-67 expression with a cutoff value of 37% (p <0.001). High EZH2 expression was correlated closely with low differentiation (p = 0.029), high CEA level (p = 0.041), T4 status (p = 0.011) and node metastasis (p =0.045). By univariate and multivariate analysis, we observed low EZH2 expression could reliably and independently predict the good response to nCRT ( p = 0.026 and p = 0.023) and down-staging ( p = 0.021 and p = 0.027). In univariate analysis, high EZH2 expression was significantly associated with poor 5-year disease-free survival (p = 0.025) and 5-year overall survival (p = 0.032). In multivariate analysis, EZH2 was a prognostic factor for 5-year DFS (HR = 2.287; 95% CI 1.137-4.602, p = 0.020) but not for 5-year OS (HR = 2.182; 95% CI 0.940-5.364, p = 0.069).
  
  
  CONCLUSIONS
  Our study revealed that low EZH2 expression in biopsy tissue might be a useful predictive factor of good tumor response to nCRT and longer 5-year DFS in patients with LARC. However this is a relatively small retrospective study, to further validate the role of EZH2 in rectal cancer, large consistent cohort studies are needed.
authors.forename: Xiangjiao
authors.initials: X
authors.lastname: Meng
authors.forename: Zhaoqin
authors.initials: Z
authors.lastname: Huang
authors.forename: Renben
authors.initials: R
authors.lastname: Wang
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Jiao
authors.forename: Huijuan
authors.initials: H
authors.lastname: Li
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Xu
authors.forename: Rui
authors.initials: R
authors.lastname: Feng
authors.forename: Kunli
authors.initials: K
authors.lastname: Zhu
authors.forename: Shumei
authors.initials: S
authors.lastname: Jiang
authors.forename: Hongjiang
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Radiation Oncology of Shandong Cancer Hospital and Institute, No, 440 Jiyan Road, Jinan, Shandong 250117, China. sdyujinming@126.com.
authors.forename: Jinming
authors.initials: J
authors.lastname: Yu
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D059248:Chemoradiotherapy / Q000379:methods; D018572:Disease-Free Survival; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D063151:Polycomb Repressive Complex 2 / Q000032:analysis / Q000096:biosynthesis*; D011379:Prognosis; D016016:Proportional Hazards Models; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2