DNA Methylation Markers Detect Prostate Cancer Field Defects

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Solution Overview

Problem

Current methods for detecting prostate cancer are inefficient, with PSA testing and biopsies often resulting in false negatives and overdiagnosis due to sampling errors, and there is a need for more accurate and less invasive diagnostic biomarkers.

Innovation Solution

A method involving the analysis of genomic DNA methylation changes in specific target regions, such as PLA2G16, CAV1, EVX1, MCF2L, FGF1, NCR2, WNT2, EXT1, and SPAG4, using techniques like pyrosequencing to detect prostate cancer field defects in human subjects, allowing for earlier and more accurate diagnosis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If PSA testing and digital rectal exam are used for early detection of prostate cancer, then screening coverage is achieved, but false negative rate increases and diagnostic accuracy decreases

Engineering Contradiction:

Improvediagnostic accuracyVSAvoidfalse negative rate

Core Design Contradiction:

ReliabilityVSLoss of information

Solution Approach 1:

The patent transitions from protein-based markers (PSA) to DNA methylation-based markers, fundamentally changing the detection parameter. This allows detection of epigenetic modifications in prostate cancer cells that are not detectable by PSA, thereby reducing false negatives and improving diagnostic accuracy through a different biological parameter

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces DNA methylation analysis as an intermediary between traditional PSA testing and prostate biopsy. This intermediate test provides more specific molecular information about prostate cancer presence and aggressiveness, reducing the need for unnecessary biopsies while improving detection accuracy

Inventive Principle:

Principle #24Intermediary (Mediator)

2Measurement precision

If multiple prostate biopsies are performed to improve detection accuracy, then diagnostic precision increases, but patient complications and procedural risks increase

Engineering Contradiction:

Improvedetection accuracyVSAvoidbiopsy complications

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent performs preliminary molecular analysis of prostate tissue (via methylation profiling) before deciding whether to proceed with invasive biopsy procedures. This preliminary action provides sufficient diagnostic information in many cases, avoiding the need for multiple biopsies and their associated complications

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent extracts and analyzes specific methylation markers (such as GSTP1, RARb, APC, RASSF1A) from prostate tissue to obtain diagnostic information without requiring extensive tissue sampling through multiple biopsies. This extraction of molecular information reduces the need for repeated invasive procedures

Inventive Principle:

Principle #2Taking out (Extraction)

3Reliability

If traditional biopsy methods are used for prostate cancer diagnosis, then histological confirmation is obtained, but sampling errors lead to overdiagnosis and underdiagnosis

Engineering Contradiction:

Improvediagnosis accuracyVSAvoidsampling error

Core Design Contradiction:

ReliabilityVSLoss of information

Solution Approach 1:

The patent changes the diagnostic parameter from histological appearance to DNA methylation patterns. This molecular parameter provides more consistent and reliable information about prostate cancer presence and characteristics, reducing the impact of sampling variability and histological interpretation errors

Inventive Principle:

Principle #35Parameter changes

4Measurement precision

If extensive tissue sampling is performed to reduce sampling errors, then diagnostic completeness improves, but procedural complexity and patient burden increase

Engineering Contradiction:

Improvediagnostic completenessVSAvoidprocedural complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent introduces methylation analysis as an intermediary diagnostic tool that provides comprehensive molecular information from minimal tissue samples. This intermediary approach achieves diagnostic completeness without requiring extensive tissue sampling or complex procedural interventions

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 enables the detection of prostate cancer with fewer biopsies and potentially non-invasive urine-based testing, reducing the risk of complications and improving diagnostic accuracy by identifying methylation changes associated with the disease.

Implementation Method 1

the methylation is quantified via pyrosequencing

Methodology Applied

Scientific EffectPyrosequencing:

Data Source

PatentUS12071672B2Unbiased DNA methylation markers define an extensive field defect in histologically normal prostate tissues associated with prostate cancer: new biomarkers for men with prostate cancer

Publication Date: 2024.08.27 WISCONSIN ALUMNI RES FOUND

AI summary

A method of detecting the presence of a prostate cancer field defect in a human subject. The method includes (a) obtaining genomic DNA from the human subject and (b) determining methylation status in at least one target region selected from the group consisting of PLA2G16, CAV1, EVX1, MCF2L, FGF1, NCR2, WNT2, EXT1, and SPAG4, wherein methylation changes indicate the presence of prostate cancer or a prostate cancer field defect, wherein the change is relative to tissue from a second human subject who does not have prostate cancer.