The mitochondrial apoptosis pathway is controlled by an interaction of multiple BCL-2 family proteins, and plays a key role in tumor progression and therapy responses.
Dr Andreas Lindner and colleagues assessed the prognostic potential of an experimentally validated, mathematical model of BCL-2 protein interactions (DR_MOMP) in patients with stage III colorectal cancer.
Absolute protein levels of BCL-2 family proteins were determined in primary colorectal cancer tumors collected from 128 resected, and chemotherapy-treated patients with stage III colorectal cancer.
The research team applied DR_MOMP to categorize patients as high or low risk based on model outputs, and compared model outputs with known prognostic factors.
|BCL-2-dependent signalling critically contributed to treatment responses |
The team validated DR_MOMP signatures on protein of 156 patients with colorectal cancer from the Cancer Genome Atlas (TCGA) project.
High-risk stage III patients identified by DR_MOMP had an approximately 5-fold increased risk of death compared with patients identified as low risk.
The researchers found that DR_MOMP signature ranked highest among all molecular and pathological features analyzed.
The prognostic signature was validated in the TCGA colon adenocarcinoma (COAD) cohort.
The research team observed that DR_MOMP also further stratified patients identified by supervised gene expression risk scores into low-risk and high-risk categories.
BCL-2-dependent signalling critically contributed to treatment responses in consensus molecular subtypes 1 and 3, linking for the first time specific molecular subtypes to apoptosis signalling.
Dr Lindner's team concludes, "DR_MOMP delivers a system-based biomarker with significant potential as a prognostic tool for stage III colorectal cancer that significantly improves established histopathological risk factors."