SDC2 Methylation Detection Reagent for Colorectal Cancer Screening

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Solution Overview

Problem

Current methods for detecting colorectal cancer, such as fecal occult blood testing and enteroscopy, face challenges including low specificity, sensitivity, and patient discomfort, while molecular detection in excrement samples suffers from interference and reduced sensitivity and specificity compared to tissue samples.

Innovation Solution

A tumor molecular diagnostic reagent using excrement as a sample, specifically targeting the SDC2 gene methylation, which maintains high sensitivity and specificity similar to tissue samples, utilizing magnetic bead capturing and methylation-specific PCR techniques.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If fecal occult blood testing is used to detect colorectal cancer, then the detection can be performed quickly and clearly with semiquantitative results, but the specificity is poor and false positive rate is high (30 percent)

Engineering Contradiction:
Improvedetection speedVSAvoidspecificity
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The invention changes the detection parameter from hemoglobin (blood component) to DNA methylation status of specific genes (e.g., NDRG4, BMP3, SFRP2). This parameter change transforms the detection from protein-based occult blood testing to molecular-based methylation detection, thereby improving specificity while maintaining the non-invasive nature of fecal sampling

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention introduces specific molecular markers (methylated DNA sequences of tumor-suppressor genes) as intermediaries to detect colorectal cancer. These methylation-specific DNA sequences serve as more reliable mediators compared to hemoglobin, reducing false positives caused by dietary factors while preserving the convenience of fecal sample collection

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If fecal occult blood testing is used to detect colorectal cancer, then the results can be obtained quickly, but the sensitivity is low and can only detect when bleeding amount is more than 90 ug/ml

Engineering Contradiction:
Improvedetection speedVSAvoidsensitivity
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The invention changes the detection target from hemoglobin concentration to DNA methylation presence/absence. Methylation is an early epigenetic event in carcinogenesis that occurs before significant bleeding or tumor formation, thereby increasing sensitivity to detect cancers at earlier stages while maintaining rapid detection capability

Inventive Principle:
Principle #35Parameter changes

3Reliability

If enteroscopy is used to examine intestinal lesions, then the diagnosis is effective and reliable with ability to detect and treat lesions, but the examination is energy-consuming, time-consuming, and causes pain to the patient

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidpatient comfort
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The invention extracts the diagnostic function from the invasive enteroscopy procedure and transfers it to a non-invasive fecal sample analysis. By detecting tumor-specific methylation patterns in fecal DNA, the system achieves reliable diagnosis without requiring bowel preparation, anesthesia, or physical insertion of scopes, thereby eliminating patient discomfort while maintaining diagnostic accuracy

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention creates a molecular copy of the tumor's genetic signature (methylation pattern) that can be detected in fecal samples. This molecular copy serves as a surrogate marker for the actual tumor, allowing diagnosis without direct visualization or physical examination of the intestinal tract

Inventive Principle:
Principle #26Copying

4Reliability

If enteroscopy is used to examine intestinal lesions, then the diagnosis is effective and reliable, but the examination cost is high and it is hard to popularize in large scale

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidcost-effectiveness
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The invention employs disposable, low-cost reagents for DNA extraction and methylation detection from fecal samples. These inexpensive chemical reagents can be used in high-throughput settings without the need for expensive, specialized equipment or highly trained operators, making the technology cost-effective and suitable for large-scale screening programs

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

5Ease of operation

If molecular detection in excrement samples is performed, then the detection can be performed without tissue sampling trauma, but the detection sensitivity and specificity are reduced compared to tissue samples due to interference from excrement components

Engineering Contradiction:
Improvesampling convenienceVSAvoiddetection sensitivity
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The invention extracts and isolates DNA from the complex excrement matrix using selective DNA extraction methods. By separating the target DNA molecules from interfering substances (proteins, lipids, bacteria, food debris), the system recovers high-quality DNA suitable for sensitive methylation detection, thereby maintaining sampling convenience while improving detection precision

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention introduces specific methylation-sensitive enzymes and antibodies as intermediaries that selectively recognize and bind to methylated DNA sequences. These intermediaries enable specific detection of tumor-related methylation patterns even in the presence of excrement components, thereby maintaining both sampling convenience and detection sensitivity

Inventive Principle:
Principle #24Intermediary (Mediator)

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

The reagent achieves reliable detection of colorectal cancer with high sensitivity (87%) and specificity (98%) in excrement samples, enabling convenient and pain-free diagnosis, and the ability to detect both left and right colon tumors and precancerous adenomas.

Implementation Method 1

utilizing magnetic bead capturing

Methodology Applied
Scientific EffectMagnetic separation: Magnetism

Implementation Method 2

methylation-specific PCR techniques

Methodology Applied
Scientific EffectPolymerase chain reaction:

Implementation Method 3

specifically targeting the SDC2 gene methylation

Methodology Applied
Scientific EffectDNA methylation:

Data Source

PatentEP3425055B1Molecular detection/diagnosis reagent for tumor
Publication Date: 2021.07.07 CREATIVE BIOSCIENCES (GUANGZHOU) CO LTD
  • EP3425055B1 patent drawingFigure 1A~2B
  • EP3425055B1 patent drawingFigure 3A~4B
  • EP3425055B1 patent drawingFigure 5

AI summary

The present invention discloses a tumor molecular detection/diagnostic reagent, which takes excrement as a detection sample and includes an SDC2 gene methylation detection reagent. The methylation level of the SDC2 gene detected in the excrement has an extremely high relevance to the onset of the colorectal cancer. The sensitivity of the SDC2 gene in the excrement is 87 percent and the specificity is up to 98 percent or even higher than that in tissue.