Biomarker Methylation Detection for Colorectal Cancer Diagnosis

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Solution Overview

Problem

Current methods for diagnosing and monitoring colorectal cancer (CRC) are invasive, lack sensitivity and specificity, and do not effectively detect early-stage tumors or assess treatment responses, particularly due to limitations in detecting methylation markers in blood samples.

Innovation Solution

A method using a biomarker profile comprising PROM1, SARP1, and MSF1 to detect methylation status in blood samples through nucleic acid amplification, allowing for non-invasive diagnosis and monitoring of CRC stages and treatment responses by identifying amplification products specific to these markers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional surgical biopsy and imaging technologies are used for CRC diagnosis, then diagnostic capability is achieved, but patient comfort deteriorates due to invasiveness and risk of infection

Engineering Contradiction:
Improvediagnostic capabilityVSAvoidinvasiveness and infection risk
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces mechanical surgical biopsy with a molecular detection system that analyzes DNA methylation patterns in circulating tumor DNA from blood samples. This substitution eliminates the need for physical tissue sampling while maintaining diagnostic accuracy through detection of epigenetic modifications characteristic of CRC.

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

Solution Approach 2:

The patent uses circulating tumor DNA and DNA methylation patterns as intermediary markers that reflect the presence and status of colorectal cancer without requiring direct contact with the tumor. These molecular intermediaries serve as proxies that convey diagnostic information while avoiding the harms of invasive procedures.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If early stage screening methods are used for CRC detection, then patient care effectiveness is improved, but sensitivity and specificity are insufficient

Engineering Contradiction:
Improvepatient care effectivenessVSAvoidsensitivity and specificity
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent shifts from detecting bulk biomarkers to analyzing specific epigenetic parameters - DNA methylation patterns at gene promoter regions. This parameter change from general biomarker presence to specific methylation status provides higher measurement precision for early CRC detection, enabling differentiation between early-stage tumors and normal tissue with greater accuracy.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent focuses on specific local regions of the genome - promoter regions of tumor suppressor genes - where methylation changes are most informative for CRC diagnosis. By concentrating analysis on these locally significant epigenetic modifications rather than genome-wide changes, the method achieves superior sensitivity and specificity for early detection.

Inventive Principle:
Principle #3Local quality

3Measurement precision

If tumor biopsy is used for methylation marker detection, then diagnostic accuracy is improved, but applicability is limited due to invasive nature

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidapplicability
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent develops a blood-based assay that can universally detect CRC-related methylation patterns across all patients regardless of tumor location, stage, or prior treatment. This single blood test methodology replaces multiple specialized biopsy procedures, making the diagnostic approach broadly applicable to all CRC patients while maintaining high diagnostic accuracy.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent uses circulating tumor DNA in blood as a copy or proxy for the genetic material in the primary tumor. This molecular copy contains the same epigenetic information as the original tumor tissue, allowing accurate diagnosis without needing to physically access or biopsy the primary tumor site.

Inventive Principle:
Principle #26Copying

4Reliability

If invasive diagnostic procedures are used for CRC staging and monitoring, then treatment planning capability is improved, but patient compliance deteriorates

Engineering Contradiction:
Improvetreatment planning capabilityVSAvoidpatient compliance
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent enables self-service monitoring where patients can have their CRC status monitored through routine blood draws that are minimally invasive and can be performed in outpatient settings. This approach allows patients to actively participate in their own disease monitoring without requiring complex hospital-based procedures, thereby improving compliance while maintaining treatment planning capability.

Inventive Principle:
Principle #25Self-service

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 method provides a sensitive and specific means for diagnosing CRC, monitoring disease progression, and evaluating treatment effectiveness by detecting methylation changes in blood samples, offering a patient-friendly and clinically effective approach.

Implementation Method 1

detecting altered methylation level of genes in a specific biomarker profile

Methodology Applied
Scientific EffectMethylation:

Implementation Method 2

subjecting the blood sample to conditions that allow nucleic acid amplification to produce amplification products specific to the methylation status

Methodology Applied
Scientific EffectNucleic acid amplification:

Data Source

PatentUS10155991B2Biomarkers for use in colorectal cancer
Publication Date: 2018.12.18 XIA XUELIANG JAMES

AI summary

The present invention provides assays, methods and kits that may be used to assess colorectal cancer (CRC) in a subject in relation to diagnosis, prognosis and treatment evaluation, using blood samples.