Colorectal Cancer Screening via Stool DNA Methylation Analysis

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Solution Overview

Problem

Current diagnostic methods for colorectal cancer are invasive, expensive, and have low uptake due to their complexity, making it difficult to effectively screen for adenomas or adenocarcinomas, as they rely on observer-defined risk factors prone to error and lack sensitivity for early detection.

Innovation Solution

A method involving the assessment of DNA methylation status in specific genomic regions, such as those defined by Hg19 coordinates and their upstream sequences, to identify changes indicative of large intestine neoplasms, using a panel of differentially methylated genes for screening and monitoring.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current diagnostic methods (colonoscopy, invasive procedures) are used, then diagnostic accuracy is improved, but patient comfort and ease of operation deteriorate due to invasiveness

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidpatient comfort
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent replaces mechanical/invasive diagnostic procedures (colonoscopy, biopsy) with a molecular biology-based detection system that analyzes DNA methylation patterns in stool samples. This substitution eliminates the need for invasive mechanical intervention while maintaining diagnostic accuracy through epigenetic marker detection.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent uses stool samples as an intermediary medium to indirectly detect colorectal neoplasia. Instead of directly examining the colon through invasive procedures, the system analyzes DNA methylation markers present in stool, serving as a non-invasive proxy that correlates with colorectal tissue status.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If current diagnostic methods are used, then diagnostic capability is improved, but device complexity and cost increase

Engineering Contradiction:
Improvediagnostic capabilityVSAvoidmethod complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the diagnostic process into distinct molecular steps: DNA extraction from stool samples, bisulfite conversion to differentiate methylated cytosines, PCR amplification of specific gene regions, and detection of methylation patterns. This segmentation creates a modular, standardized workflow that reduces overall complexity compared to invasive procedures.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent detects disease state by measuring changes in DNA methylation parameters (methylation levels at specific CpG sites in genes like NDRG4, SDC2, and CAHXI). This parameter-based detection approach transforms a complex diagnostic problem into a quantifiable molecular measurement that can be processed through standardized laboratory procedures.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If current diagnostic methods are used, then detection capability is improved, but loss of time and productivity deteriorate due to low uptake and procedural time

Engineering Contradiction:
Improvedetection capabilityVSAvoidscreening time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent performs preliminary detection of colorectal neoplasia through stool-based methylation analysis before invasive procedures are needed. By screening for epigenetic markers in stool samples, the system identifies at-risk individuals who then require further investigation, reducing unnecessary invasive procedures and optimizing resource allocation.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent enables self-service sampling where patients can collect stool samples at home without requiring clinical intervention. This eliminates the need for scheduled colonoscopy appointments and procedural time, allowing patients to perform the initial screening step independently while maintaining high detection capability through methylation marker analysis.

Inventive Principle:
Principle #25Self-service

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach allows for a simple and accurate screening method that can detect predisposition or onset of large intestine neoplasms by identifying higher methylation levels in biological samples, enhancing diagnostic precision and reducing the need for invasive procedures.

Implementation Method 1

changes to DNA methylation levels are indicative of the onset or predisposition to the onset of a neoplasm

Methodology Applied
Scientific EffectDNA methylation:

Data Source

PatentEP3508589B1Epigenetic markers of colorectal cancers and diagnostic methods using the same
Publication Date: 2023.03.01 CLINICAL GENOMICS PTY LTD
  • EP3508589B1 patent drawingFigure 1(a)~1(b)
  • EP3508589B1 patent drawingFigure 1(c)~1(d)
  • EP3508589B1 patent drawingFigure 1(e)~1(f)

AI summary

A method of screening for the onset of a large intestine neoplasm or monitoring the progress of a neoplasm in an individual, said method comprising assessing the methylation status of a DNA region defined by Hgl9 coordinates chr6:391752..411443 and 2kb upstream of the transcription start site of IRF4, in a biological sample from said individual wherein a higher level of methylation of said DNA region relative to control levels is indicative of a large intestine neoplasm or a predisposition to the onset of a large intestine neoplasm.