Urine DNA Methylation Detection for Bladder Cancer Recurrence

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Solution Overview

Problem

Current methods for detecting bladder cancer, particularly superficial forms, are invasive, expensive, and have limited sensitivity, leading to high recurrence rates and significant healthcare costs due to the need for perpetual monitoring.

Innovation Solution

Utilizing the methylation status of specific CpG islands in DNA, especially in urine samples, as diagnostic and prognostic markers for bladder cancer, including the use of methylation-specific PCR and multiplex ligation-dependent probe amplification to detect hypermethylated CpG islands associated with bladder cancer.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If cystoscopy is used for detection of bladder cancer recurrences, then detection accuracy is improved, but patient comfort deteriorates and procedure cost increases

Engineering Contradiction:

Improvedetection accuracyVSAvoidpatient comfort

Core Design Contradiction:

Measurement precisionVSEase of operation

Solution Approach 1:

The patent uses urine as an intermediary medium to detect bladder cancer recurrences. Instead of directly examining the bladder through invasive cystoscopy, the method analyzes DNA methylation patterns in urine samples, which serve as a non-invasive proxy for detecting tumor presence and recurrence.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the mechanical invasive procedure of cystoscopy with a biochemical analysis method. By detecting methylation status of specific CpG islands in urine DNA using molecular biology techniques (PCR, bisulfite sequencing), the method substitutes mechanical visualization with chemical/biological detection.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Reliability

If cystoscopy is used for perpetual monitoring of bladder cancer patients, then recurrence detection is improved, but healthcare cost increases

Engineering Contradiction:

Improverecurrence detectionVSAvoidhealthcare cost

Core Design Contradiction:

ReliabilityVSLoss of energy

Solution Approach 1:

The patent employs inexpensive urine collection and analysis methods that can be performed repeatedly without significant cost. The use of standard molecular biology techniques on readily available urine samples provides a cost-effective alternative to expensive, repeated cystoscopy procedures.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The method enables patients to self-collect urine samples for monitoring, reducing the need for frequent hospital visits and invasive procedures. The simple urine collection process allows patients to participate in their own monitoring, reducing overall healthcare system burden.

Inventive Principle:

Principle #25Self-service

3Ease of operation

If cytology on voided urine is used for detection, then patient comfort is improved, but sensitivity deteriorates

Engineering Contradiction:

Improvepatient comfortVSAvoidsensitivity

Core Design Contradiction:

Ease of operationVSMeasurement precision

Solution Approach 1:

The patent changes the detection parameter from visual inspection of cells (cytology) to molecular analysis of DNA methylation status. By analyzing the epigenetic modifications (methylation patterns) in urine DNA rather than cellular morphology, the method achieves high sensitivity while maintaining the non-invasive urine collection approach.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent replaces conventional cytological examination with molecular biology techniques. Instead of visually assessing urine cells under a microscope, the method uses DNA extraction, bisulfite treatment, and methylation-specific PCR or sequencing to detect cancer-related epigenetic changes with higher sensitivity.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical 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

Provides a non-invasive, cost-effective method for detecting bladder cancer recurrence and progression, improving diagnostic accuracy and reducing the need for invasive procedures like cystoscopy, while also offering therapeutic targets through demethylating agents for treatment.

Implementation Method 1

the methylation of a number of specific CpG islands (CGIs) in the DNA of cells shaded in the urine of a subject is indicative of the present of a tumor

Methodology Applied

Scientific EffectMethylation:

Implementation Method 2

the use of methylation-specific PCR and multiplex ligation-dependent probe amplification to detect hypermethylated CpG islands

Methodology Applied

Scientific EffectPCR amplification:

Implementation Method 3

detection of recurrent cancer in DNA isolated from patient urine

Methodology Applied

Scientific EffectDNA extraction:

Data Source

PatentUS12529110B2Method of diagnosing bladder cancer

Publication Date: 2026.01.20 ERASMUS UNIV MEDICAL CENT ROTTERDAM ERASMUS MC

AI summary

The present invention relates to a method of diagnosing cancer in a subject comprising detecting in the DNA of said subject at least one hypermethylated CpG island associated with said cancer, wherein an elevation in the level of methylation in said CpG island of said subject, relative to the level of methylation in said CpG island of a control subject, is indicative of said CpG island being hypermethylated.