Tumor Cell Detection Using Multi-Marker Segmentation
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Solution Overview
Problem
Current methods for detecting and collecting circulating tumor cells (CTCs) from blood samples face challenges due to the low number of CTCs and interference from contaminant cells like erythrocytes and leukocytes, leading to false positives and negatives, especially with existing tumor markers like cytokeratin and EpCAM.
Innovation Solution
The development of a method using specific polypeptides and genes, such as TM4SF1, TNFRSF12A, SDC1, F3, EPHA2, and ITGA2, which are highly expressed in cancer cells, allowing for the distinction and detection of tumor cells from contaminant cells using next-generation sequencing and antibody or aptamer recognition.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If cytokeratin is used as a tumor marker for CTC detection, then epithelial tumor cells can be detected, but contaminant cells are also detected non-specifically leading to false positives
Solution Approach 1:
The patent segments the detection approach by using multiple distinct tumor markers (EpCAM, cytokeratin, CD44, CD166, CD133, CD24) rather than relying on a single marker. This segmentation allows the system to detect tumor cells through multiple independent pathways, reducing false positives from non-specific binding to any single marker while maintaining high detection accuracy for actual tumor cells.
2Productivity
If EpCAM is used as a tumor marker for CTC collection, then epithelium-derived tumor cells can be collected, but collection is limited to only part of epithelium-derived CTCs
Solution Approach 1:
The patent creates a universal detection system that functions across multiple cancer types by combining six different tumor markers, each with different expression patterns. EpCAM targets epithelium-derived CTCs, while cytokeratin, CD44, CD166, CD133, and CD24 provide additional coverage for various cancer types including breast, lung, prostate, pancreatic, and gastrointestinal cancers, making the system universally applicable.
3Measurement precision
If conventional tumor markers are used for CTC detection, then detection can be performed, but the low number of CTCs in blood makes distinction from contaminant cells difficult
Solution Approach 1:
The patent merges multiple detection methods and markers into a single integrated system. By simultaneously detecting tumor cells through six different markers (EpCAM, cytokeratin, CD44, CD166, CD133, CD24) and combining this with next-generation sequencing for genetic analysis, the system amplifies the tumor cell signal while the low abundance of contaminant cells expressing multiple markers simultaneously keeps the noise low, dramatically improving the signal-to-noise ratio.
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 accurate detection and collection of tumor cells from blood samples with high specificity, improving upon the limitations of existing methods by targeting a wider range of cancer types and reducing false positives and negatives.
Implementation Method 1
The detection is carried out using an antibody or aptamer that specifically recognizes one or more polypeptides selected from the group consisting of (i) to (iii)
Data Source
AI summary
A method of collecting and detecting a tumor cell contained in a sample in distinction from a contaminant cell is provided. The tumor cell contained in the sample are collected and detected in distinction from the contaminant cell by detecting any of the following polypeptides or a gene encoding the polypeptide present in the sample: (i) a polypeptide containing at least the amino acid sequence of any of six sequences such as TM4SF1 (GenBank No. NP_055035.1) and TNFRSF12A (GenBank No. NP_057723.1); (ii) a polypeptide containing at least an amino acid sequence having a homology of not less than 70% to the amino acid sequence described above; and (iii) a polypeptide containing at least a splicing variant of the amino acid sequence (the amino acid sequence of (i) or (ii) described above).