Multi-Protein Stool Biomarker Panels for Early Colorectal Cancer Screening
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Solution Overview
Problem
Current stool-based screening tests for colorectal cancer, such as the fecal immunochemical test (FIT), have sub-optimal sensitivity for detecting early-stage colorectal cancer and advanced adenomas, leading to high rates of false negatives and false positives, and there is a need for alternative protein biomarkers that can improve detection accuracy.
Innovation Solution
A method for typing colorectal cancerous cells using a stool sample by determining the expression levels of a set of genes, including SERPINF2, S100A8, and HBA1, which can differentiate between cancerous and non-cancerous growths, combined with an immunochemical assay using specific antibodies to quantify protein expression molecules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If fecal immunochemical test (FIT) is used for colorectal cancer screening, then the test is non-invasive and can be performed in population-wide screening programs, but the sensitivity for detecting early-stage colorectal cancer and advanced adenomas is sub-optimal
Solution Approach 1:
The patent combines multiple protein biomarkers (hemoglobin, calprotectin, and other inflammation-related proteins) into a single screening test panel. This merging of multiple detection targets allows the test to maintain the non-invasive advantage of FIT while significantly improving sensitivity for detecting early-stage colorectal cancer and advanced adenomas through the cumulative information from multiple biomarkers.
Solution Approach 2:
The invention uses a composite approach by measuring multiple protein markers simultaneously rather than relying on a single biomarker. The combination of hemoglobin (for blood detection) with calprotectin and other inflammation-related proteins creates a composite diagnostic profile that enhances detection capability while maintaining the ease of stool-based sampling.
2Reliability
If alternative protein biomarkers are used to improve detection accuracy over FIT, then sensitivity may be improved, but the complexity of the test increases and validation becomes more difficult
Solution Approach 1:
The patent employs antibodies that can detect multiple related proteins or protein families, allowing a single reagent to serve multiple detection functions. This multi-functionality approach improves detection accuracy by capturing a broader range of biomarker variations while avoiding the need for completely separate assays for each marker, thereby controlling test complexity.
Solution Approach 2:
The invention measures multiple parameters (different protein biomarkers) simultaneously rather than relying on a single parameter. By changing from a single-biomarker approach to a multi-biomarker panel, the test achieves superior detection accuracy while using the same basic immunochemical assay platform, thus managing complexity through parameter expansion rather than methodological complexity.
3Measurement precision
If biomarker discovery is performed in tissue and cell line material first, then discriminating markers can be identified, but validation in stool samples may fail due to effects from bacterial proteases and glycosidases
Solution Approach 1:
The patent performs preliminary identification and validation of protein biomarkers directly in stool samples rather than first identifying markers in tissue/cell lines and then validating in stool. This preliminary action in the actual screening matrix (stool) accounts for the effects of bacterial proteases and glycosidases from the beginning, ensuring that identified markers are truly suitable for stool-based screening and reducing validation failure risk.
Solution Approach 2:
The invention uses stable, abundant proteins in stool samples as intermediary markers that are less susceptible to degradation by bacterial enzymes. By selecting biomarkers that are naturally resistant to bacterial protease and glycosidase activity, the patent creates a bridge between the complex stool environment and reliable detection, ensuring validation success.
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 high sensitivity and specificity for detecting early-stage colorectal cancer and advanced adenomas, reducing false negatives and false positives, and can be used for accurate staging and treatment assignment.
Implementation Method 1
an immunochemical assay using specific antibodies to quantify protein expression molecules
Data Source
Figure 1A~1C
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AI summary
The invention relates to methods for typing a sample of an individual suffering from a colorectal cancer, or suspected of suffering therefrom. A preferred sample is stool. The invention further relates to methods for determining a level of expression of at least two extracted protein expression molecules in stool,, based on the quantified reaction products, and to methods of assigning treatment to an individual that was typed as suffering from colorectal cancer according to the invention.