Colorectal Cancer Screening Panel Using SERPINF2 Biomarkers

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Solution Overview

Problem

Current screening methods for colorectal cancer, such as the immunochemical fecal occult blood test, have limitations in sensitivity and do not effectively detect all colon tumors, highlighting the need for additional biomarkers that can improve early detection and identification of high-risk adenomas.

Innovation Solution

The method involves screening stool samples for specific biomarkers like SERPINF2 using targeted mass spectrometry or antibody-based assays, which can indicate the presence of high-risk colorectal adenomas or adenocarcinomas, leveraging a panel of proteins identified through in-depth proteomics analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If the immunochemical fecal occult blood test (FIT) is used for colorectal cancer screening, then the screening can be performed in a non-invasive manner, but the sensitivity is insufficient because not all colon tumors bleed

Engineering Contradiction:

Improvesensitivity of screeningVSAvoidability to detect all tumor types

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent combines multiple biomarkers (SERPINF2, S100A8, S100A9, and other proteins) into a multi-marker screening panel that detects various tumor characteristics beyond just bleeding. This merging of multiple detection targets increases sensitivity while maintaining the non-invasive stool-based approach, resolving the contradiction between reliable detection and comprehensive tumor type coverage.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The screening method is designed to detect multiple different tumor types and characteristics through a single multi-marker assay. The panel includes markers for bleeding tumors, non-bleeding tumors, and different stages of neoplastic progression, making the test universally applicable to diverse colorectal pathologies while maintaining non-invasive operation.

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Reliability

If additional protein markers are added to improve detection sensitivity, then more tumor characteristics can be detected, but the complexity of the screening test increases

Engineering Contradiction:

Improvedetection sensitivityVSAvoidcomplexity of screening test

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs mass spectrometry technology to detect multiple protein markers simultaneously in a highly automated manner. This substitution of manual or sequential testing with automated mass spectrometry-based detection increases sensitivity through multi-marker analysis while reducing operational complexity through automation, resolving the contradiction between enhanced detection capability and test complexity.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Ease of manufacture

If biomarkers are discovered using tissue and cell line material, then the discovery process is well-established, but the biomarkers may not be stable in the fecal environment used for actual screening

Engineering Contradiction:

Improveease of biomarker discoveryVSAvoidstability of biomarker in fecal sample

Core Design Contradiction:

Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The patent performs proteomics analysis directly on stool samples, allowing the fecal environment itself to reveal which biomarkers are naturally stable and detectable in this matrix. This self-service approach identifies biomarkers that have proven stability in the actual screening medium, resolving the contradiction between ease of discovery using established tissue-based methods and stability in the fecal environment.

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

This approach enhances the sensitivity and specificity of colorectal cancer screening by detecting biomarkers stable in the fecal environment, potentially improving early detection and diagnosis beyond existing methods.

Implementation Method 1

screening a stool sample obtained from an individual for one or more biomarkers comprising serpin peptidase inhibitor, clade F, member 2 (SERPINF2)

Methodology Applied

Scientific EffectMass spectrometry:

Implementation Method 2

the stool sample is screened for the one or more biomarkers comprising SERPINF2 using targeted mass spectrometry

Methodology Applied

Scientific EffectTargeted mass spectrometry:

Implementation Method 3

the stool sample is screened for the one or more biomarkers comprising SERPINF2 using a binding agent capable of binding to the one or more biomarkers

Methodology Applied

Scientific EffectAntibody binding:

Data Source

PatentEP3671215B1biomarkers

Publication Date: 2023.03.29 STICHTING VUMC

Figure 1A~1B
Figure 2A~2B
Figure 2C~2D

AI summary

The invention provides a method for screening for colorectal cancer, the method comprising: screening a biological sample from an individual for one or more biomarkers selected from the group defined in Table 1 and/or Table 6, wherein the presence of or increased expression of the one or more biomarkers relative to a control sample is indicative that the individual is at risk of suffering from or is suffering from colorectal cancer. The invention also provides an array and kit suitable for use in the methods of the invention, methods of treating colorectal cancer and therapeutic agents for use in methods of treating cancer.