title: Apoptosome-dependent caspase activation proteins as prognostic markers in Stage II and III colorectal cancer.
abstract: BACKGROUND
  Critical to successful execution of mitochondrial-mediated apoptosis is apoptosome formation and subsequent activation of caspases. Defects in this pathway have an important role in colorectal carcinogenesis and chemoresistance; therefore, the expression of apoptosome-associated proteins may be associated with clinical outcome and response to chemotherapy.
  
  
  METHODS
  Here we performed a systematic analysis of the immunohistochemical expression of the key proteins involved in apoptosome-dependent caspase activation (APAF1, Pro-caspases 9 and 3, SMAC, and XIAP) in a cohort of Stage II and III colorectal cancer patients from a Phase III trial of adjuvant 5-fluorouracil-based chemotherapy vs postoperative observation alone.
  
  
  RESULTS
  Survival analysis indicated that of the apoptosome-associated proteins examined here, Pro-caspase 3 and APAF1 have potential clinical utility as predictive markers in Stage II and III colorectal cancer, respectively. Interestingly, we identified APAF1 staining to be associated with better recurrence-free and overall survival in patients receiving chemotherapy.
  
  
  CONCLUSIONS
  These studies reveal the importance of the apoptosome-dependent caspase activation pathway, specifically Pro-caspase 3 and APAF1 proteins, for predicting both prognosis and response to therapy.
authors.affiliation: Department of Physiology and Medical Physics, Dublin, Ireland.
authors.forename: S
authors.initials: S
authors.lastname: Hector
authors.forename: S
authors.initials: S
authors.lastname: Conlon
authors.forename: J
authors.initials: J
authors.lastname: Schmid
authors.forename: P
authors.initials: P
authors.lastname: Dicker
authors.forename: R J
authors.initials: RJ
authors.lastname: Cummins
authors.forename: C G
authors.initials: CG
authors.lastname: Concannon
authors.forename: P G
authors.initials: PG
authors.lastname: Johnston
authors.forename: E W
authors.initials: EW
authors.lastname: Kay
authors.forename: J H M
authors.initials: JH
authors.lastname: Prehn
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis; D053478:Apoptosomes / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D004789:Enzyme Activation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D046888:Tissue Array Analysis
chemical_list: D053478:Apoptosomes; D020169:Caspases; D002955:Leucovorin; D005472:Fluorouracil