Epigenetic Biomarker Panel for Bladder Cancer Detection

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Solution Overview

Problem

Current methods for detecting bladder cancer are inadequate due to low sensitivity and specificity, particularly for low-grade tumors, and lack effective non-invasive strategies for early detection and monitoring, leading to high morbidity and mortality.

Innovation Solution

The identification and use of epigenetic biomarkers such as GDF15, HSPA2, and VIM, detected through methylation analysis in tissue and urine samples, to accurately diagnose and predict bladder cancer, distinguishing it from other urological cancers with high sensitivity and specificity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional urine cytology and cystoscopy are used for bladder cancer detection, then the diagnostic method is non-invasive and relatively simple, but the sensitivity is low especially for low grade tumors

Engineering Contradiction:
Improvedetection sensitivityVSAvoiddiagnostic method complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent changes the detection parameter from conventional cytological examination to epigenetic methylation status analysis. By detecting methylation levels of specific genes (GDF15, HSPA2, TMEFF2, VIM) in urine samples, the method achieves superior sensitivity (94%) and specificity (100%) compared to traditional cytology, while maintaining the non-invasive nature of urine-based testing

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replaces the mechanical/cytological examination system with a molecular biology-based detection system. Instead of visually examining cells under a microscope, the method uses methylation-specific PCR and bisulfite sequencing to detect epigenetic modifications, substituting a more sophisticated molecular detection mechanism for the conventional mechanical approach

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Reliability

If existing BICa markers are used for detection, then the cost is higher compared with routine urinary cytology, but the predictive power is low

Engineering Contradiction:
Improvepredictive powerVSAvoidcost
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent shifts from detecting protein markers or genetic mutations to detecting epigenetic methylation patterns. This parameter change enables the use of urine samples with methylation-specific PCR, achieving high predictive power (94% sensitivity, 100% specificity) at a cost comparable to or lower than existing marker-based tests, while providing superior diagnostic accuracy

Inventive Principle:
Principle #35Parameter changes

3Reliability

If frequent cystoscopy monitoring is performed for early-stage BlCa patients, then the detection capability is maintained, but the cost management becomes one of the most costly cancer diseases

Engineering Contradiction:
Improvedetection capabilityVSAvoidcost
Core Design Contradiction:
ReliabilityVSLoss of energy

Solution Approach 1:

The patent extracts the detection function from the invasive cystoscopy procedure and transfers it to a simple urine-based methylation assay. By taking out the essential detection capability and implementing it through a low-cost urine test that measures epigenetic markers, the system maintains high detection capability while eliminating the high costs associated with frequent cystoscopy procedures

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs a disposable urine sample-based detection system that replaces the expensive, resource-intensive cystoscopy procedure. The methylation-specific PCR assay using urine DNA is a low-cost, single-use test that can be performed repeatedly without the high costs of repeated cystoscopies, making it an economically sustainable monitoring solution

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

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 biomarker panel achieves 100% sensitivity and specificity in tissue samples and 94% sensitivity and 100% specificity in urine samples, effectively identifying bladder cancer and differentiating it from other urological tumors, enabling early detection and monitoring.

Implementation Method 1

Gene methylation levels were quantified in four bladder cancer cell lines, 50 bladder cancer tissues, 20 normal bladder mucosas, and urine sediments from 51 bladder cancer patients and 20 healthy donors

Methodology Applied
Scientific EffectDNA methylation:

Data Source

PatentEP2630261B1Methods and biomarkers for detection of bladder cancer
Publication Date: 2019.04.17 UNIV OSLO HF
  • EP2630261B1 patent drawingFigure 1
  • EP2630261B1 patent drawingFigure 2
  • EP2630261B1 patent drawingFigure 3A~3D

AI summary

The invention relates to methods and biomarkers (e.g., epigenetic biomarkers) for detection of bladder cancer in biological samples (e.g., tissue samples, urine samples, urine sediments). In some embodiments, methods and biomarkers of the present invention find use in discriminating between bladder cancer, prostate cancer and renal epithelial tumors.