CTC Subgroup Identification via Immunophenotypic Marker Panels
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Solution Overview
Problem
Current methods for detecting and characterizing circulating tumor cells (CTCs) in patients with solid tumors, such as hepatocellular carcinoma (HCC) and non-small cell lung cancer, are inefficient due to the rarity and heterogeneity of CTCs, leading to challenges in diagnosis, prognosis, and monitoring treatment effectiveness.
Innovation Solution
A method for identifying and characterizing CTC subgroups in biological samples by isolating peripheral blood mononuclear cells, depleting hematopoietic cells, and testing for epithelial, mesenchymal, and transition markers, allowing for the determination of CTC subgroup composition and monitoring changes over time, which can be used as biomarkers for diagnosis and treatment monitoring.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current CTC detection methods are used, then detection can be performed, but detection precision and reliability are insufficient due to CTC rarity and heterogeneity
Solution Approach 1:
The patent segments the heterogeneous CTC population into distinct subgroups based on marker expression profiles (e.g., EpCAM+, CK+, CD45- for epithelial CTCs; CD133+ for stem-like CTCs; vimentin+ for mesenchymal CTCs). This segmentation allows precise characterization of different CTC subsets, improving both detection precision and reliability by addressing CTC heterogeneity systematically.
Solution Approach 2:
The patent changes the detection parameters by using multiple immunophenotypic markers simultaneously (EpCAM, cytokeratins, CD45, CD133, vimentin, N-cadherin) rather than single-marker approaches. This multi-parameter strategy enables reliable identification of diverse CTC subgroups, transforming the detection capability from insufficient to robust.
2Measurement precision
If multiple markers are used to identify CTC subgroups, then identification accuracy improves, but method complexity increases
Solution Approach 1:
The patent employs a universal immunophenotypic panel that can identify multiple CTC subgroups simultaneously using a standardized set of markers (EpCAM, CK, CD45, CD133, vimentin, N-cadherin). This multi-functional approach allows a single method to characterize various CTC subsets (epithelial, mesenchymal, stem-like, hybrid) without requiring separate assays, thereby improving identification accuracy while managing complexity through standardization.
3Loss of information
If CTC subgroups are characterized in detail, then diagnostic and prognostic value improves, but time and resources required increase
Solution Approach 1:
The patent performs preliminary immunophenotypic characterization of CTCs using a standardized marker panel before further analysis. By pre-defining CTC subgroups based on established marker profiles (e.g., EpCAM+CK+CD45- for epithelial, CD133+ for stem-like), the method captures critical diagnostic and prognostic information early in the workflow, reducing subsequent analysis time while maximizing information extraction from the CTC population.
Data Source
AI summary
The invention generally relates to the field of individualized medicine. It is a kind of liquid biopsy for individualizing and monitoring treatment in patients with tumors and for diagnosis of tumors. The invention relates to a method for identifying and characterizing subpopulations (subgroups) of circulating tumor cells (CTCs) in a population of CTCs in a biological sample, preferably in a blood sample of the patient. The invention also relates to the quantification of the respective subgroups of CTCs in the population of CTCs in the biological sample. The invention further relates to the use of the method for diagnosis and monitoring of tumors, decisions relating to treatment, surveillance of treatment and prognosis, in particular for all kinds of solid tumors. The invention further relates to the use of the identified CTC subgroups as biomarkers for diagnosis, prognosis and therapeutic treatment. In addition, the invention relates to diagnostic devices and test kits for application of the method of the invention.