Related Experiment Video
Updated: Nov 26, 2025
Detection of a CDH1 Rare Transcript Variant in Fresh-frozen Gastric Cancer Tissues by Chip-based Digital PCR
Published on: February 5, 2018
Ultrasensitive Gastric Cancer Circulating Tumor Cellular CLDN18.2 RNA Detection Based on a Molecular Beacon
Linyang Fan1, Xiaoyi Chong2, Minzhi Zhao3
1School of Life Science, Beijing Institute of Technology, Beijing 100081, P. R. China.
Abstract:
Gastric cancer (GC) is a major global cancer burden, and only HER2-targeted therapies have been approved in first line clinical therapy. CLDN18.2 has been regarded as a potential therapeutic target for gastrointestinal tumors, and global clinical trials have been in process. Hence, the precise, efficient, and noninvasive detection of CLDN18.2 expression is important for the effective application of this attractive target. A high similarity of protein sequence between CLDN18.1 and -18.2 made RNA become more suitable for the detection of CLDN18.2 expression. In this study, CLDN18.2 molecular beacon (MB) with a stem-loop hairpin structure was optimized by phosphorothioate and 2'-O-methyl for stability and efficiency. The MB could recognize CLDN18.2 RNA rapidly. Its resolution and selectivity has been verified in several model cells, demonstrating that MB can distinguish CLDN18.2 expression in several model cells. Furthermore, it was applied successfully to the circulating tumor cell (CTC) assay. The concordance in the expression of CLDN18.2 between CTCs and tissue biopsy is 100% (negative: 3 vs 3; positive: 7 vs 7), indicating that CLDN18.2 RNA detection in CTCs based on a MB will be a promising approach for searching potential patients to CLDN 18.2 targeted drug.
Insights
A novel molecular beacon (MB) accurately detects CLDN18.2 RNA in circulating tumor cells (CTCs). This noninvasive method shows 100% concordance with tissue biopsy, aiding patient selection for CLDN18.2 targeted therapies.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Gastric cancer (GC) presents a significant global health challenge.
- Current first-line therapies for GC are limited, with HER2-targeted treatments being the only approved option.
- Claudin 18.2 (CLDN18.2) is emerging as a promising therapeutic target for gastrointestinal tumors, necessitating precise detection methods.
Purpose of the Study:
- To develop a precise, efficient, and noninvasive method for detecting CLDN18.2 expression.
- To optimize a molecular beacon (MB) for stable and efficient recognition of CLDN18.2 RNA.
- To evaluate the utility of MB-based CLDN18.2 RNA detection in circulating tumor cells (CTCs) for patient selection.
Main Methods:
- Optimized a CLDN18.2-specific molecular beacon (MB) using phosphorothioate and 2'-O-methyl modifications for enhanced stability and efficiency.
- Verified the resolution and selectivity of the MB in distinguishing CLDN18.2 expression across various model cells.
- Applied the MB assay to detect CLDN18.2 RNA in circulating tumor cells (CTCs) and compared results with tissue biopsies.
Main Results:
- The optimized MB demonstrated rapid and specific recognition of CLDN18.2 RNA.
- The MB successfully distinguished CLDN18.2 expression levels in different cell models.
- A 100% concordance rate was observed between CLDN18.2 RNA detection in CTCs and corresponding tissue biopsies (7 positive, 3 negative).
Conclusions:
- MB-based detection of CLDN18.2 RNA in CTCs is a highly accurate and noninvasive approach.
- This method offers a promising strategy for identifying patients eligible for CLDN18.2 targeted therapies.
- The high concordance validates CTCs as a reliable source for assessing CLDN18.2 expression relevant to targeted treatment selection.
