Robust performance of the methylated NTMT1 and MAP3K14-AS1 dual-target test for colorectal cancer detection in plasma by using sense-antisense and dual-MGB probe technique

Autor: Yanteng Zhao, Zhijie Wang, Qiuning Yu, Xin Liu, Xue Liu, Shuling Dong, Xianping Lv, Yu Bai, Shaochi Wang
Rok vydání: 2022
Popis: Background Blood-based methylation tests showed higher patient compliance and convenience than colonoscopy and stool DNA tests for colorectal cancer (CRC) detection. This study aimed to enhance the performance of plasma markers to detect CRCs using sense-antisense and dual-MGB probe (SADMP) technique. Method The current study consisted of 3 phases. The first phase was identifying eligible methylation markers. The second phase was assay development that incorporated the SADMP technique into methylation-specific PCR to enhance the target sensitivities in detecting plasma methylation signals. The third phase was assessing the test performance for CRC detection in training and validation cohorts. Results Hypermethylated NTMT1 and MAP3K14-AS1 were found in multiple CRC cohorts. The SADMP technique showed an approximately 2-fold increase in detecting methylation signals than single-strand and single-MGB probe techniques. The established MethyDT test obtained an average sensitivity of 84.47% for CRC detection, higher than any single target alone without a significant attenuation of specificity (average specificities of 91.81% for NTMT1 and 96.93% for MAP3K14-AS1 vs. 89.76% for MethyDT). For early (I-II) and late- (III-IV) stage CRC, the test sensitivities were 82.61% and 88.64%, respectively, in validation cohort. Meanwhile, the test sensitivity was independent of patient age and gender. Conclusion The SADMP technique enhanced the detection of methylation signals, and the MethyDT test showed potential utility as a promising noninvasive tool for CRC detection.
Databáze: OpenAIRE