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.

CONCLUSION:

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: S Hector, S Conlon, J Schmid, P Dicker, R J Cummins, C G Concannon, P G Johnston, E W Kay, J H M Prehn
• Journal: British journal of cancer (Br J Cancer) Vol. 106 Issue 9 Pg. 1499-1505 (Apr 24 2012) ISSN: 1532-1827 [Electronic] England
• PMID: 22481083 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosomes
• Caspases
• Leucovorin
• Fluorouracil

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Apoptosis
• Apoptosomes (metabolism)
• Caspases (metabolism)
• Chemotherapy, Adjuvant
• Clinical Trials, Phase III as Topic
• Colorectal Neoplasms (drug therapy, metabolism, pathology)
• Enzyme Activation
• Female
• Fluorouracil (administration & dosage)
• Humans
• Immunoenzyme Techniques
• Leucovorin (administration & dosage)
• Male
• Middle Aged
• Neoplasm Staging
• Prognosis
• Tissue Array Analysis