OPLAH and ADHFE1 DMR Kit for Noninvasive Colorectal Screening
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Solution Overview
Problem
Current colorectal cancer screening methods, such as colonoscopy, fecal occult blood detection, and tumor markers, are invasive, have low sensitivity, or produce false positives, necessitating the development of a more accurate and non-invasive early screening method.
Innovation Solution
The use of differentially methylated regions (DMRs) of the OPLAH and ADHFE1 genes, detected through a kit involving primers and probes, to assess methylation status in stool samples, combined with fecal occult blood detection for enhanced sensitivity and specificity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If colonoscopy is used for colorectal cancer detection, then detection accuracy is improved, but invasiveness and complexity increase
Solution Approach 1:
The patent uses stool samples as an intermediary medium to detect colorectal cancer markers. Instead of directly examining the colon through colonoscopy, the method detects methylation markers (SEPT9, SDC2, NDRG4, PPP2R5C) in stool DNA, which contains shed cellular material from the colon. This intermediary approach maintains detection accuracy while eliminating the invasiveness of colonoscopy.
2Ease of operation
If fecal occult blood detection is used, then non-invasiveness is improved, but sensitivity and specificity deteriorate
Solution Approach 1:
The patent changes the detection parameter from fecal occult blood (hemoglobin) to DNA methylation status. By detecting methylation markers in stool DNA rather than blood in stool, the method achieves both non-invasiveness and high sensitivity. The methylation detection can identify cancer cells even when bleeding is minimal or absent, overcoming the sensitivity limitations of fecal occult blood tests.
3Ease of operation
If tumor markers CEA and CA19-9 are used, then simplicity is improved, but specificity and sensitivity deteriorate
Solution Approach 1:
The patent applies local quality by detecting methylation status at specific genomic loci (SEPT9, SDC2, NDRG4, PPP2R5C) rather than using broad-spectrum tumor markers. Each marker is selected for its specific association with colorectal cancer, providing high specificity. The stool-based approach maintains simplicity while the targeted methylation detection achieves superior specificity and sensitivity compared to traditional tumor markers.
4Measurement precision
If multiple methylation markers are combined for detection, then sensitivity is improved, but device complexity increases
Solution Approach 1:
The patent segments the detection system into separate components: stool sample collection, DNA extraction, methylation-specific PCR for each marker (SEPT9, SDC2, NDRG4, PPP2R5C), and result analysis. This segmentation allows each marker to be detected independently using standardized protocols, maintaining high sensitivity through multi-marker analysis while managing complexity through modular, systematic detection of individual markers rather than requiring a single complex integrated system.
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 method provides high sensitivity and specificity for detecting colorectal cancer and precancerous lesions, improving detection rates and reducing invasiveness, with sensitivity reaching 86.62% and specificity of 92.78% for colorectal cancer.
Implementation Method 1
DNA methylation is an important gene expression regulation mechanism that can regulate gene expression and silencing, and has a significant impact on the occurrence and development of tumors. Abnormal methylation of cancer-related genes often occurs in the early stages of cancer, so DNA methylation signals are considered to be potential early screening markers for tumors.
Data Source
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AI summary
Provided are a combination of differentially methylated regions, a kit, and use thereof. The combination of differentially methylated regions comprises the following differentially methylated regions: (1) chr8: 145106171-145107467 and (2) chr8:67344198-67345563. The combination of differentially methylated regions can be used for effective detection of colorectal cancer or precancerous lesions of colorectal cancer, or for evaluating prognostic risks of colorectal cancer patients, exhibiting high sensitivity and specificity.