ANKRD13B and FOXF2 Methylation Detection for Early Cancer Diagnosis

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Solution Overview

Problem

Existing methods for detecting cancer through methylation analysis in liquid biopsies face challenges in distinguishing between low levels of methylated tumor DNA and high backgrounds of non-tumor DNA, leading to sensitivity and specificity issues, especially in early-stage cancers where tumor DNA release is minimal.

Innovation Solution

The use of ANKRD13B and FOXF2 markers, which are not methylated in healthy subjects, allows for sensitive and specific detection of cancer by identifying methylation patterns in blood or blood-derived samples, using oligonucleotides such as primers, blockers, or probes complementary to these markers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If methylation analysis is performed on circulating tumor DNA in liquid biopsy, then cancer detection capability is improved, but sensitivity deteriorates due to low tumor DNA release in early-stage cancers

Engineering Contradiction:

Improvecancer detection capabilityVSAvoidsensitivity

Core Design Contradiction:

ReliabilityVSMeasurement precision

Solution Approach 1:

The patent applies local quality by selecting specific genomic regions (ANKRD13B and FOXF2 genes) that exhibit localized methylation changes in cancer cells. Instead of analyzing the entire genome, the method focuses on specific CpG sites within these genes that show distinct methylation patterns in tumor-derived DNA compared to normal DNA, enabling sensitive detection of early-stage cancers

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent utilizes parameter changes by detecting methylation status (methylated vs. unmethylated) at specific CpG sites within the ANKRD13B and FOXF2 genes. This epigenetic parameter change serves as a biomarker to distinguish tumor DNA from normal DNA in circulating cell-free DNA, providing high sensitivity for early cancer detection

Inventive Principle:

Principle #35Parameter changes

2Reliability

If methylation analysis is performed to detect cancer, then detection capability is improved, but specificity deteriorates due to high background of non-tumor DNA

Engineering Contradiction:

Improvecancer detection capabilityVSAvoidspecificity

Core Design Contradiction:

ReliabilityVSMeasurement precision

Solution Approach 1:

The patent extracts the distinguishing feature by isolating and analyzing only the methylation status of specific CpG sites within the ANKRD13B and FOXF2 genes from the complex mixture of circulating cell-free DNA. This extraction of specific epigenetic information from the high background of non-tumor DNA enables highly specific cancer detection

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies inversion by using the absence of methylation in normal cells as the baseline and detecting the presence of methylation as the cancer-specific signal. Traditional approaches looked for hypomethylation in cancer, but this method reverses the logic by targeting hypermethylated regions in cancer cells, thereby achieving high specificity

Inventive Principle:

Principle #13The other way round (Inversion)

3Measurement precision

If selective amplification of methylated tumor DNA is performed, then detection sensitivity is improved, but method complexity increases

Engineering Contradiction:

Improvedetection sensitivityVSAvoidmethod complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by performing bisulfite conversion of the DNA sample before amplification. This chemical treatment converts unmethylated cytosines to uracils while leaving methylated cytosines unchanged, creating sequence differences that enable subsequent selective amplification of methylated tumor DNA through methylation-specific PCR with designed primers

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses methylation-specific blockers as intermediaries to achieve selective amplification. These blocker oligonucleotides bind to unmethylated DNA sequences and prevent primer binding or extension, thereby allowing only methylated tumor DNA to be amplified. This intermediary mechanism simplifies the detection process while maintaining high 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

This approach enhances the sensitivity and specificity of cancer detection, enabling early diagnosis and improved treatment strategies by identifying methylated genomic DNA of ANKRD13B and FOXF2 in various cancers, including stomach, liver, colon, ovary, esophagus, bladder, and prostate cancers.

Implementation Method 1

using oligonucleotides such as primers, blockers, or probes complementary to these markers

Methodology Applied

Scientific EffectBase pairing:

Data Source

PatentUS20250333796A1Methods for detecting cpg methylation of tumor-derived DNA in blood samples

Publication Date: 2025.10.30 NEW DAY DIAGNOSTICS LLC

AI summary

The present invention relates to the field of pharmacogenomics and in particular to detecting the presence or absence of methylated ANKRD13B and/or FOXF2 DNA derived from a tumor in blood or blood-derived samples or in other body fluids that contain DNA released from a tumor. This detection is useful for a minimally invasive diagnosis of cancers and the invention provides methods and oligonucleotides suitable for this purpose.