Caspase modelling to predict personalised risk in stage III colorectal cancer (CRC) patients.

11592Background: Aberrant apoptosis is coupled with chemotherapy-resistance. Here, we applied a mathematical model of downstream apoptosis execution (APOPTO-CELL) and investigated its suitability as a prognostic tool in stage III CRC patients. Methods: Patient-specific apoptosis susceptibility (AS) was simulated by APOPTO-CELL from the protein expressions of procaspase-3 (PC3), procaspase-9, SMAC and XIAP quantified by reverse phase protein array on FFPE primary tumour tissue from a prospective multi-centre cohort of n = 120 CRC patients treated with 5-fluorouracil-based chemotherapy. Associations with disease-free survival (DFS) and overall survival (OS) and other clinicopathological features (CPFs) were analysed by Kaplan-Meier estimates, Cox regression models and Random Forest (RF) machine learning. Findings were validated in a colon adenocarcinoma cohort (TCGA COAD, n = 134) where the association of AS with CRC consensus molecular subtypes (CMS) was also explored. Results: Apoptosis-resistant patients...