Type

Journal Article

Authors

Jochen H M Prehn
Sandra Van Schaeybroeck
Pierre Laurent-Puig
Bryan T Hennessy
Elaine W Kay
Deborah A McNamara
Sophie Camilleri-Broët
Manuel Salto-Tellez
Patrick G Johnston
Richard Wilson
and 12 others

Subjects

Medicine & Nursing

Topics
bcl 2 colorectal cancer system analysis colorectal cancer crc risk analysis risk factors bcl 2 family cancer patients

BCL-2 system analysis identifies high-risk colorectal cancer patients. (2016)

Abstract The mitochondrial apoptosis pathway is controlled by an interaction of multiple BCL-2 family proteins, and plays a key role in tumour progression and therapy responses. We assessed the prognostic potential of an experimentally validated, mathematical model of BCL-2 protein interactions (DR_MOMP) in patients with stage III colorectal cancer (CRC). Absolute protein levels of BCL-2 family proteins were determined in primary CRC tumours collected from n=128 resected and chemotherapy-treated patients with stage III CRC. We applied DR_MOMP to categorise patients as high or low risk based on model outputs, and compared model outputs with known prognostic factors (T-stage, N-stage, lymphovascular invasion). DR_MOMP signatures were validated on protein of n=156 patients with CRC from the Cancer Genome Atlas (TCGA) project. High-risk stage III patients identified by DR_MOMP had an approximately fivefold increased risk of death compared with patients identified as low risk (HR 5.2, 95% CI 1.4 to 17.9, p=0.02). The DR_MOMP signature ranked highest among all molecular and pathological features analysed. The prognostic signature was validated in the TCGA colon adenocarcinoma (COAD) cohort (HR 4.2, 95% CI 1.1 to 15.6, p=0.04). 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_MOMP delivers a system-based biomarker with significant potential as a prognostic tool for stage III CRC that significantly improves established histopathological risk factors.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Jochen H M Prehn, Sandra Van Schaeybroeck, Pierre Laurent-Puig, Bryan T Hennessy, Elaine W Kay, Deborah A McNamara, Sophie Camilleri-Broët, Manuel Salto-Tellez, Patrick G Johnston, Richard Wilson and 12 others

Experts in our system

1
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
2
Bryan T Hennessy
Royal College of Surgeons in Ireland
Total Publications: 33
 
3
Elaine W Kay
Royal College of Surgeons in Ireland
Total Publications: 157
 
4
Deborah A McNamara
Royal College of Surgeons in Ireland
Total Publications: 17