title: Expression of the calpain system is associated with poor clinical outcome in gastro-oesophageal adenocarcinomas.
abstract: BACKGROUND
  Surgery is critical in the management of gastro-oesophageal cancer, and the addition of neo-adjuvant chemotherapy has proved to be of benefit. The calpain system has been implicated in tumour progression and response to various anti-cancer therapies, and therefore expression of the system was determined in this tumour type.
  
  
  METHODS
  Two cohorts of gastro-oesophageal adenocarcinomas were investigated for calpain-1, calpain-2, calpain-9 and calpastatin expression using conventional immunohistochemistry. 88 patients who received neo-adjuvant chemotherapy and 140 patients who received surgery alone were investigated using a tissue microarray approach.
  
  
  RESULTS
  Calpain-1, calpain-2 and calpastatin expression was associated with adverse cancer-specific survival in the neo-adjuvant cohort (P = 0.004, P = 0.001 and P = 0.012 respectively); which remained significant in multivariate analysis (Hazard ratio (HR) = 0.337; 95% confidence interval (CI) = 0.140-0.81; P = 0.015, HR = 0.375; 95% CI = 0.165-0.858; P = 0.020 and HR = 0.481; 95% CI = 0.257-0.900; P = 0.022 respectively). Calpain-1 and calpastatin expression was also associated with adverse cancer specific survival in the primary surgery cohort (P = 0.001 and P = 0.013 respectively); which remained significant in multivariate analysis (HR = 0.309; 95% CI = 0.159-0.601; P = 0.001 and HR = 0.418; 95% CI = 0.205-0.850; P = 0.016 respectively). Calpain-9 expression was not associated with cancer-specific survival in the neo-adjuvant and primary surgery cohorts.
  
  
  CONCLUSIONS
  Determining the expression levels of calpain-1, calpain-2 and calpastatin may provide clinically relevant prognostic information for gastro-oesophageal adenocarcinomas; these findings warrant further studies in larger cohorts of patients.
authors: Academic Oncology, School of Molecular Medical Sciences, University of Nottingham, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, NG5 1PB, UK.
authors: Sarah J
authors: SJ
authors: Storr
authors: Xuan
authors: X
authors: Pu
authors: Jillian
authors: J
authors: Davis
authors: Dileep
authors: D
authors: Lobo
authors: Alex M
authors: AM
authors: Reece-Smith
authors: Simon L
authors: SL
authors: Parsons
authors: Srinivasan
authors: S
authors: Madhusudan
authors: Stewart G
authors: SG
authors: Martin
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002154:Calpain / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D006801:Humans; D053208:Kaplan-Meier Estimate; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D046888:Tissue Array Analysis / Q000379:methods; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; C033668:calpastatin; D002154:Calpain