title: MRE11 and ATM Expression Levels Predict Rectal Cancer Survival and Their Association with Radiotherapy Response.
abstract: BACKGROUND
  Aberrant expression of DNA repair proteins is associated with poor survival in cancer patients. We investigated the combined expression of MRE11 and ATM as a predictive marker of response to radiotherapy in rectal cancer.
  
  
  METHODS
  MRE11 and ATM expression were examined in tumor samples from 262 rectal cancer patients who underwent surgery for rectal cancer, including a sub-cohort of 54 patients who were treated with neoadjuvant radiotherapy. The relationship between expression of the two-protein panel and tumor regression grade (TRG) was assessed by Mann-Whitney U test and receiver operating characteristics area under curve (ROC-AUC) analysis. The association between expression of the two-protein panel and clinicopathologic variables and survival was examined by Kaplan-Meier methods and Cox regression analysis.
  
  
  RESULTS
  A high score for two-protein combined expression in the tumor center (TC) was significantly associated with worse disease-free survival (DFS) (P = 0.035) and overall survival (OS) (P = 0.003) in the whole cohort, and with DFS (P = 0.028) and OS (P = 0.024) in the neoadjuvant subgroup (n = 54). In multivariate analysis, the two-protein combination panel (HR = 2.178, 95% CI 1.115-4.256, P = 0.023) and perineural invasion (HR = 2.183, 95% CI 1.222-3.899, P = 0.008) were significantly associated with DFS. Using ROC-AUC analysis of good versus poor histological tumor response among patients treated preoperatively with radiotherapy, the average ROC-AUC was 0.745 for the combined panel, 0.618 for ATM alone, and 0.711 for MRE11 alone.
  
  
  CONCLUSIONS
  The MRE11/ATM two-protein panel developed in this study may have clinical value as a predictive marker of tumor response to neoadjuvant radiotherapy, and a prognostic marker for disease-free and overall survival.
authors.affiliation: School of Medicine, Western Sydney University, Penrith, New South Wales, Australia.
authors.forename: Vincent
authors.initials: V
authors.lastname: Ho
authors.affiliation: School of Medicine, Western Sydney University, Penrith, New South Wales, Australia.|Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia.
authors.forename: Liping
authors.initials: L
authors.lastname: Chung
authors.affiliation: School of Medicine, Western Sydney University, Penrith, New South Wales, Australia.
authors.forename: Maxine
authors.initials: M
authors.lastname: Revoltar
authors.affiliation: Department of Medical Oncology, Liverpool Hospital, Liverpool, New South Wales, Australia.|South Western Sydney Clinical School, University of New South Wales, Liverpool, New South Wales, Australia.
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Lim
authors.affiliation: Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia.|Department of Anatomical Pathology, Liverpool Hospital, Liverpool, New South Wales, Australia.
authors.forename: Thein-Ga
authors.initials: TG
authors.lastname: Tut
authors.affiliation: School of Medicine, Western Sydney University, Penrith, New South Wales, Australia.|Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia.
authors.forename: Askar
authors.initials: A
authors.lastname: Abubakar
authors.affiliation: School of Medicine, Western Sydney University, Penrith, New South Wales, Australia.|Department of Anatomical Pathology, Liverpool Hospital, Liverpool, New South Wales, Australia.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Henderson
authors.affiliation: Department of Medical Oncology, Liverpool Hospital, Liverpool, New South Wales, Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Chua
authors.affiliation: Department of Medical Oncology, Liverpool Hospital, Liverpool, New South Wales, Australia.
authors.forename: Weng
authors.initials: W
authors.lastname: Ng
authors.affiliation: Department of Radiation Oncology, Liverpool Hospital, Liverpool, New South Wales, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Lee
authors.affiliation: School of Medicine, Western Sydney University, Penrith, New South Wales, Australia.|Department of Medical Oncology, Liverpool Hospital, Liverpool, New South Wales, Australia.|Discipline of Medical Oncology, School of Medicine, Western Sydney University, Liverpool, New South Wales, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: De Souza
authors.affiliation: Department of Surgery, Bankstown Hospital, Bankstown, New South Wales, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Morgan
authors.affiliation: School of Medicine, Western Sydney University, Penrith, New South Wales, Australia.|Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia.|Department of Anatomical Pathology, Liverpool Hospital, Liverpool, New South Wales, Australia.|Discipline of Pathology, School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia.
authors.forename: C Soon
authors.initials: CS
authors.lastname: Lee
authors.affiliation: School of Medicine, Western Sydney University, Penrith, New South Wales, Australia.|Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia.|Department of Anatomical Pathology, Liverpool Hospital, Liverpool, New South Wales, Australia.|Discipline of Pathology, School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia.
authors.forename: Joo-Shik
authors.initials: JS
authors.lastname: Shin
mesh_terms: D000368:Aged; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D000076228:MRE11 Homologue Protein; D008297:Male; D011379:Prognosis; D012372:ROC Curve; D012004:Rectal Neoplasms / Q000473:pathology* / Q000532:radiotherapy; D016019:Survival Analysis
chemical_list: D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D000076228:MRE11 Homologue Protein