DNA Methylation Marker for Non-Invasive Cancer T-Status Staging
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Solution Overview
Problem
Existing cancer diagnosis methods, particularly for lung cancer, are hindered by resource shortages and delays, leading to inadequate staging and delayed therapy initiation, especially during healthcare crises like pandemics, necessitating a non-invasive, resource-independent method for early detection and prioritization of high-stage cancer patients.
Innovation Solution
A method utilizing the methylation level of a specific genomic DNA site (DMP corresponding to Illumina probe ID cg01218619) to distinguish between TNM-classification T1 and T3/T4 status in cancer patients, combined with machine learning and additional data evaluation, allowing for early diagnosis and prioritization of patients for rapid therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If invasive histopathology and imaging are used to evaluate tumor T-status, then measurement precision is improved, but device complexity and resource requirements worsen
Solution Approach 1:
The patent extracts the essential diagnostic information needed for T-status determination from complex multimodal evaluations and concentrates it into a single DNA methylation marker assay. By measuring methylation levels at specific CpG sites in genomic DNA, the method isolates the critical diagnostic signal from the complexity of imaging and histopathology, achieving accurate tumor staging through a simplified single-marker approach
Solution Approach 2:
The patent replaces mechanical and invasive diagnostic procedures (imaging, biopsy, histopathology) with a molecular biology-based assay. The DNA methylation analysis uses biochemical methods (bisulfite conversion, PCR amplification, methylation-specific binding) to substitute for complex medical imaging and surgical biopsy procedures, reducing device complexity while maintaining diagnostic accuracy
2Measurement precision
If invasive biopsy and histopathology are performed, then measurement precision is improved, but loss of time worsens due to procedural delays
Solution Approach 1:
The patent performs preliminary diagnostic action by analyzing DNA methylation patterns in easily obtainable samples (blood, saliva, or tissue) to predict T-status before invasive procedures are undertaken. The methylation marker analysis provides advance diagnostic information that can guide subsequent clinical decisions, reducing the time needed for definitive staging by performing the critical assessment on non-invasive or minimally invasive samples first
Solution Approach 2:
The patent creates a molecular copy or surrogate marker (DNA methylation pattern) that reflects the tumor's T-status without requiring direct examination of the tumor tissue through biopsy. The methylation signature serves as a copy of the tumor's pathological state, allowing diagnosis and staging to be performed on peripheral blood or other accessible samples, thereby eliminating time loss associated with scheduling and performing invasive biopsies
3Measurement precision
If resource-intensive multimodal evaluation is used, then measurement precision is improved, but productivity worsens due to resource shortages
Solution Approach 1:
The patent extracts the essential diagnostic capability from resource-intensive multimodal evaluations and concentrates it into a single, streamlined DNA methylation assay. By focusing on one or more specific CpG site methylation markers, the method eliminates the need for multiple imaging studies, biopsy procedures, and histopathology consultations, thereby increasing diagnosis throughput while maintaining TNM-staging accuracy
Solution Approach 2:
The patent changes the diagnostic parameter from complex structural and histological assessments to a simple molecular measurement (methylation level at specific CpG sites). This parameter change transforms the diagnostic process from a resource-intensive multimodal evaluation requiring multiple specialists and equipment to a single molecular assay that can be performed with standardized laboratory equipment, significantly improving productivity and diagnosis throughput
4Ease of operation
If non-invasive liquid biopsy is used, then ease of operation is improved, but measurement precision worsens due to limited histopathological information
Solution Approach 1:
The patent replaces mechanical histopathological assessment (microscopic examination of tissue sections) with a molecular biology-based detection system. The DNA methylation assay uses biochemical methods to detect and quantify methylation patterns that are characteristic of different T-status levels, substituting visual-histological evaluation with molecular signal detection, thereby maintaining measurement precision while achieving ease of operation through non-invasive sampling
Solution Approach 2:
The patent changes the measurement parameter from histological features (tissue architecture, cell morphology, invasion patterns visible under microscope) to epigenetic markers (methylation levels at specific CpG sites in tumor-associated genes). This parameter change allows the assessment of tumor infiltration status through molecular patterns that can be detected in circulating DNA from liquid biopsy, maintaining diagnostic precision while enabling simple non-invasive sample collection
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
Facilitates early diagnosis and prioritization of high-stage cancer patients, reducing hospital burden and enabling timely therapy selection through non-invasive sample collection, such as a blood draw, even in resource-constrained settings.
Implementation Method 1
determining the methylation level of a methylation site in a genomic DNA molecule
Data Source
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AI summary
The present invention relates to a method for diagnosing, detecting or monitoring a cancer disease in a subject, comprising determining the methylation level of a methylation site in a genomic DNA derived from the subject's sample, wherein said methylation site comprises the differentially methylated position (DMP) corresponding to Illumina probe ID cg01218619 (SEQ ID NO: 1). Also envisaged is a corresponding kit, a method of enriching DNA molecules derived from a subject's sample and the use of the DMP for diagnosing, detecting or monitoring a cancer disease.