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 20 January 2018

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News

Identifying high-risk colorectal cancer patients

This month's issue of Gut identifies system-based biomarker with significant potential as a prognostic tool for stage III colorectal cancer.

News image

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
Gut

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."

Gut 2017;66:2141-2148
12 December 2017

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