CMS Gene Probe Classifier for FFPE Colorectal Cancer Typing
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current assays for classifying colorectal cancer, such as Oncotype DX and Coloprint, require fresh frozen tissue and struggle with sample degradation in formalin-fixed paraffin-embedded (FFPE) samples, limiting their practical application and accuracy in clinical settings.
Innovation Solution
A gene set and customized list of gene probes are provided for classifying colorectal cancer into four consensus molecular subtypes (CMS) using either FF or FFPE samples, utilizing a weighted support vector machine for accurate classification and nanostring probes to measure gene expression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If fresh frozen tissue is used for gene expression analysis, then measurement precision is improved, but ease of operation deteriorates due to tissue handling requirements and limited clinical applicability
Solution Approach 1:
The patent changes the physical state parameter of the tissue sample from fresh frozen to formalin-fixed paraffin-embedded (FFPE), which is more stable and easier to handle in clinical settings. This parameter change allows the tissue to maintain integrity without requiring specialized freezing and storage infrastructure, thereby improving ease of operation while preserving sufficient gene expression information for classification.
2Ease of operation
If existing classification assays are used, then ease of operation is improved, but measurement precision deteriorates due to limited prognostic accuracy and inability to identify high-risk patients
Solution Approach 1:
The patent segments the patient population into distinct molecular subtypes (CMS1, CMS2, CMS3, CMS4) based on gene expression patterns. This segmentation allows for more precise prognostic classification compared to existing assays, enabling identification of high-risk patients who would benefit from intensified therapy while maintaining ease of operation through a standardized assay protocol.
3Ease of operation
If simplified treatment regimens are used for stage III patients, then ease of operation is improved, but reliability deteriorates due to inadequate treatment of high-risk patients
Solution Approach 1:
The patent applies local quality by tailoring treatment intensity to specific molecular subtypes rather than applying uniform treatment to all stage III patients. High-risk subtypes receive intensified adjuvant chemotherapy while lower-risk subtypes receive standard or reduced therapy, optimizing treatment effectiveness for each patient group while maintaining operational simplicity through clear classification criteria.
Data Source
AI summary
Provided herein is a consensus molecular subtype (CMS) classifier for colorectal cancer patients. Also provided are methods of using the classifier to identify a clinically beneficial therapeutic regime for each patient as well as methods of treating a patient accordingly Custom Nanostring code sets, which work on formalin-fixed, paraffin-embedded samples, are provide for use in determining the CMS for a colorectal cancer patient.