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Adaptation of Semiautomated Circulating Tumor Cell CTC Assays for Clinical and Preclinical Research Applications
Published on: February 28, 2014
Combined Molecular and Morphological Imaging of CTCs for HER2-Targeted Chemotherapy Guidance
Haimeng Pei1, Zhaojun Han1, Dexin Du1
1College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, People's Republic of China.
Abstract:
Since biomolecules change dynamically with tumor evolution and drug treatment, it is necessary to confirm target molecule expression in real time for effective guidance of subsequent chemotherapy treatment. However, current methods to confirm target proteins require complex processing steps and invasive tissue biopsies, limiting their clinical utility for targeted treatment monitoring. Here, CTCs, as a promising liquid biopsy source, were used to molecularly characterize the target protein HER2. To accurately identify CTCs, we specifically proposed a combined molecular and morphological imaging method, rather than using specific biomarker alone or morphology analysis, we identified CTCs as CK19+/CD45-/HE+. On the basis of the accurate identification of CTCs, we further analyzed the target protein HER2 in clinical patients at the single-CTC level. Comparative analysis of the clinical results of patient pathological tissue and paired blood samples showed that CTCs had a heterogeneous HER2 expression at the single-cell level and showed results inconsistent with the immunohistochemistry results in some cases. CTC-based analysis could help clinicians have a more comprehensive understanding of patient target protein expression. We believe that CTC-based target protein studies are of great significance for the precise management of targeted therapy.
Insights
Circulating tumor cells (CTCs) offer a novel approach for real-time monitoring of HER2 expression, crucial for guiding cancer therapy. This liquid biopsy method reveals heterogeneous HER2 expression at the single-cell level, improving targeted treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- Dynamic changes in biomolecules during tumor evolution and treatment necessitate real-time monitoring of target protein expression.
- Current methods for protein confirmation, such as tissue biopsies, are invasive and complex, limiting their clinical application for targeted therapy monitoring.
- Circulating tumor cells (CTCs) present a viable alternative as a liquid biopsy source for non-invasive molecular characterization.
Purpose of the Study:
- To develop and validate a method for real-time molecular characterization of the HER2 protein in circulating tumor cells (CTCs).
- To assess the clinical utility of CTCs for monitoring HER2 expression heterogeneity at the single-cell level.
- To compare CTC-based HER2 expression analysis with traditional immunohistochemistry (IHC) methods using patient samples.
Main Methods:
- Proposed a combined molecular and morphological imaging technique for accurate identification of CTCs, defined as CK19+/CD45-/HE+.
- Analyzed HER2 protein expression in individual CTCs isolated from blood samples of clinical patients.
- Compared CTC-derived HER2 expression data with results from paired patient pathological tissue biopsies.
Main Results:
- Accurate identification of CTCs was achieved using the combined imaging approach.
- CTC analysis revealed heterogeneous HER2 expression at the single-cell level.
- Discrepancies between CTC-based HER2 expression and IHC results were observed in some cases, highlighting the limitations of traditional methods.
Conclusions:
- CTC-based analysis provides a more comprehensive understanding of patient-specific target protein expression compared to conventional methods.
- Single-cell level HER2 expression analysis in CTCs is significant for the precise management of targeted cancer therapy.
- This liquid biopsy approach holds great promise for improving the efficacy and personalization of cancer treatment strategies.
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