A novel xenonucleic acid-mediated molecular clamping technology for early colorectal cancer screening.

<h4>Background</h4>Colorectal cancer (CRC) is one of the leading causes of cancer-related death. Early detection is critical to reduce CRC morbidity and mortality. In order to meet this need, we developed a molecular clamping assay called the ColoScape TM assay for early colorectal cance...

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Autores principales:	Qing Sun, Larry Pastor, Jinwei Du, Michael J Powell, Aiguo Zhang, Walter Bodmer, Jianzhong Wu, Shu Zheng, Michael Y Sha
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6bc54573175a459991b18a9f502219dd
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spelling	oai:doaj.org-article:6bc54573175a459991b18a9f502219dd2021-12-02T20:13:50ZA novel xenonucleic acid-mediated molecular clamping technology for early colorectal cancer screening.1932-620310.1371/journal.pone.0244332https://doaj.org/article/6bc54573175a459991b18a9f502219dd2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0244332https://doaj.org/toc/1932-6203<h4>Background</h4>Colorectal cancer (CRC) is one of the leading causes of cancer-related death. Early detection is critical to reduce CRC morbidity and mortality. In order to meet this need, we developed a molecular clamping assay called the ColoScape TM assay for early colorectal cancer diagnostics.<h4>Methods</h4>Nineteen mutations in four genes (APC, KRAS, BRAF and CTNNB1) associated with early events in CRC pathogenesis are targeted in the ColoScapeTM assay. Xenonucleic Acid (XNA)-mediated qPCR clamping technology was applied to minimize the wild-type background amplification in order to improve assay sensitivity of CRC mutation detection. The assay analytical performance was verified and validated, cfDNA and FFPE CRC patient samples were evaluated, and an ROC curve was applied to evaluate its performance.<h4>Results</h4>The data showed that the assay analytical sensitivity was 0.5% Variant Allele Frequency, corresponding to ~7-8 copies of mutant DNA with 5 ng total DNA input per test. This assay is highly reproducible with intra-assay CV of <3% and inter-assay CV of <5%. We have investigated 380 clinical samples including plasma cfDNA and FFPE samples from patients with precancerous and different stages of CRC. The preliminary assay clinical specificity and sensitivity for CRC cfDNA were: 100% (95% CI, 80.3-97.5%) and 92.2% (95% CI, 94.7-100%), respectively, with AUC of 0.96; 96% specificity (95% CI, 77.6-99.7%) and 92% sensitivity (95% CI, 86.1-95.6%) with AUC of 0.94 for CRC FFPE; 95% specificity (95% CI, 82.5%-99.1%) and 62.5% sensitivity (95% CI, 35.8%-83.7%) with AUC of 0.79 for precancerous lesions cfDNA.<h4>Conclusions</h4>The XNA-mediated molecular clamping assay is a rapid, precise, and sensitive assay for the detection of precancerous lesions cfDNA and CRC cfDNA or FFPE samples.Qing SunLarry PastorJinwei DuMichael J PowellAiguo ZhangWalter BodmerJianzhong WuShu ZhengMichael Y ShaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0244332 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Qing Sun Larry Pastor Jinwei Du Michael J Powell Aiguo Zhang Walter Bodmer Jianzhong Wu Shu Zheng Michael Y Sha A novel xenonucleic acid-mediated molecular clamping technology for early colorectal cancer screening.
description	<h4>Background</h4>Colorectal cancer (CRC) is one of the leading causes of cancer-related death. Early detection is critical to reduce CRC morbidity and mortality. In order to meet this need, we developed a molecular clamping assay called the ColoScape TM assay for early colorectal cancer diagnostics.<h4>Methods</h4>Nineteen mutations in four genes (APC, KRAS, BRAF and CTNNB1) associated with early events in CRC pathogenesis are targeted in the ColoScapeTM assay. Xenonucleic Acid (XNA)-mediated qPCR clamping technology was applied to minimize the wild-type background amplification in order to improve assay sensitivity of CRC mutation detection. The assay analytical performance was verified and validated, cfDNA and FFPE CRC patient samples were evaluated, and an ROC curve was applied to evaluate its performance.<h4>Results</h4>The data showed that the assay analytical sensitivity was 0.5% Variant Allele Frequency, corresponding to ~7-8 copies of mutant DNA with 5 ng total DNA input per test. This assay is highly reproducible with intra-assay CV of <3% and inter-assay CV of <5%. We have investigated 380 clinical samples including plasma cfDNA and FFPE samples from patients with precancerous and different stages of CRC. The preliminary assay clinical specificity and sensitivity for CRC cfDNA were: 100% (95% CI, 80.3-97.5%) and 92.2% (95% CI, 94.7-100%), respectively, with AUC of 0.96; 96% specificity (95% CI, 77.6-99.7%) and 92% sensitivity (95% CI, 86.1-95.6%) with AUC of 0.94 for CRC FFPE; 95% specificity (95% CI, 82.5%-99.1%) and 62.5% sensitivity (95% CI, 35.8%-83.7%) with AUC of 0.79 for precancerous lesions cfDNA.<h4>Conclusions</h4>The XNA-mediated molecular clamping assay is a rapid, precise, and sensitive assay for the detection of precancerous lesions cfDNA and CRC cfDNA or FFPE samples.
format	article
author	Qing Sun Larry Pastor Jinwei Du Michael J Powell Aiguo Zhang Walter Bodmer Jianzhong Wu Shu Zheng Michael Y Sha
author_facet	Qing Sun Larry Pastor Jinwei Du Michael J Powell Aiguo Zhang Walter Bodmer Jianzhong Wu Shu Zheng Michael Y Sha
author_sort	Qing Sun
title	A novel xenonucleic acid-mediated molecular clamping technology for early colorectal cancer screening.
title_short	A novel xenonucleic acid-mediated molecular clamping technology for early colorectal cancer screening.
title_full	A novel xenonucleic acid-mediated molecular clamping technology for early colorectal cancer screening.
title_fullStr	A novel xenonucleic acid-mediated molecular clamping technology for early colorectal cancer screening.
title_full_unstemmed	A novel xenonucleic acid-mediated molecular clamping technology for early colorectal cancer screening.
title_sort	novel xenonucleic acid-mediated molecular clamping technology for early colorectal cancer screening.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/6bc54573175a459991b18a9f502219dd
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A novel xenonucleic acid-mediated molecular clamping technology for early colorectal cancer screening.

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