TY - JOUR
T1 - Ultrasensitive Gastric Cancer Circulating Tumor Cellular CLDN18.2 RNA Detection Based on a Molecular Beacon
AU - Fan, Linyang
AU - Chong, Xiaoyi
AU - Zhao, Minzhi
AU - Jia, Fei
AU - Wang, Zihua
AU - Zhou, Ying
AU - Lu, Xiao
AU - Huang, Qiongrong
AU - Li, Ping
AU - Yang, Yanlian
AU - Hu, Zhiyuan
AU - Li, Qin
AU - Zhang, Xiaotian
AU - Shen, Lin
N1 - Publisher Copyright:
© 2020 American Chemical Society.
PY - 2021/1/19
Y1 - 2021/1/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85098995981&partnerID=8YFLogxK
U2 - 10.1021/acs.analchem.0c04055
DO - 10.1021/acs.analchem.0c04055
M3 - Article
AN - SCOPUS:85098995981
SN - 0003-2700
VL - 93
SP - 665
EP - 670
JO - Analytical Chemistry
JF - Analytical Chemistry
IS - 2
ER -
