Phage Microarray Autoantibody Panel for Colorectal Cancer Diagnosis

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current diagnostic methods for colorectal cancer (CRC) are inadequate due to the lack of specific biomarkers, leading to late diagnosis and ineffective screening, with existing biomarkers like CEA, CA19.9, and CA125 being non-specific and invasive, necessitating the development of a simple and non-invasive method for early detection, prognosis, and monitoring of CRC progression.

Innovation Solution

The use of phage microarrays to identify autoantibodies in serum samples, specifically targeting sequences homologous to NHSL1, GRN, MST1, SULF1, SREBF2, and GTF2i proteins, which combine to predict CRC with 72% sensitivity and 87% specificity, allowing for the discrimination of disease stages and monitoring of treatment efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional biomarkers (CEA, CA19.9, CA125) are used for CRC diagnosis, then the diagnostic method is simple and widely available, but the specificity and sensitivity are insufficient leading to late diagnosis

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidmethod complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the diagnostic approach by using a panel of multiple autoantibodies (against SULF1, MST1, and other tumor-associated antigens) rather than relying on a single biomarker. This segmentation allows for more precise detection of CRC through combined analysis of multiple autoimmune responses, thereby improving diagnostic accuracy while maintaining clinical feasibility

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent employs autoantibodies that serve multiple functions: they not only detect the presence of CRC but also differentiate between early and late stages of the disease, and can monitor treatment response. This multi-functionality of the autoantibody panel resolves the contradiction by providing comprehensive diagnostic information without requiring multiple separate tests

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

2Measurement precision

If invasive diagnostic tests (colonoscopy) are performed early, then diagnostic accuracy improves, but patient comfort and ease of operation deteriorate

Engineering Contradiction:
Improveearly detection capabilityVSAvoidpatient comfort
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent uses autoantibodies in serum as intermediary markers that reflect the presence and stage of CRC without requiring direct visualization or intervention in the colon. These autoantibodies serve as mediators between the tumor and the diagnostic test, enabling early detection through simple blood draws rather than invasive colonoscopy, thus maintaining high detection accuracy while significantly improving patient comfort

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If a panel of multiple autoantibodies is used, then diagnostic specificity and sensitivity improve, but the complexity of the diagnostic method increases

Engineering Contradiction:
Improvediagnostic validityVSAvoidassay complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent merges the detection of multiple autoantibodies (against SULF1, MST1, and other tumor-associated antigens) into a single integrated diagnostic assay. By combining these detections and analyzing the pattern of autoimmune responses together, the method achieves high diagnostic reliability through multiple markers while presenting a unified, streamlined testing approach that does not require separate complex procedures for each autoantibody

Inventive Principle:
Principle #5Merging (Combining)

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 provides a simple, non-invasive method for diagnosing and monitoring CRC progression, improving early detection and prognosis by utilizing a panel of autoantibodies with high predictive accuracy, enabling effective treatment evaluation and survival prediction.

Implementation Method 1

contacting a sample from a subject with an antibody capturing entity (ACE), wherein said ACE is an ACE comprising the amino acid sequence shown in SEQ ID NO: 4 or a peptide or protein having at least 90% sequence identity with respect to SEQ ID NO: 4 and that is recognized by an autoantibody against SEQ ID NO: 4; and detecting the formation of a complex between an autoantibody and said ACE

Methodology Applied
Scientific EffectAntibody-antigen binding:

Data Source

PatentEP2570813B1Method for the diagnosis/prognosis of colorectal cancer
Publication Date: 2020.06.17 CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS (CSIC)
  • EP2570813B1 patent drawingFigure 1
  • EP2570813B1 patent drawingFigure 2A~2B
  • EP2570813B1 patent drawingFigure 3A

AI summary

The present invention relates to a method for obtaining useful data for the diagnosis, prognosis or monitoring of colorectal cancer (CRC) progression, to a method for the diagnosis of CRC, to a method for the prognosis of CRC and to a kit for carrying out said methods.