Literature DB >> 33393992

Giant Magnetoresistive Nanosensor Analysis of Circulating Tumor DNA Epidermal Growth Factor Receptor Mutations for Diagnosis and Therapy Response Monitoring.

Jared C Nesvet1, Katie A Antilla2, Danielle S Pancirer3, Alexander X Lozano4,5, Jordan S Preiss3, Weijie Ma6, Aihua Fu7, Seung-Min Park8,9, Sanjiv S Gambhir8,9,10, Alice C Fan11, Joel W Neal3,11, Sukhmani K Padda3,11, Millie Das3,11,12, Tianhong Li6, Heather A Wakelee3,11, Shan X Wang4,10,13.   

Abstract

BACKGROUND: Liquid biopsy circulating tumor DNA (ctDNA) mutational analysis holds great promises for precision medicine targeted therapy and more effective cancer management. However, its wide adoption is hampered by high cost and long turnaround time of sequencing assays, or by inadequate analytical sensitivity of existing portable nucleic acid tests to mutant allelic fraction in ctDNA.
METHODS: We developed a ctDNA Epidermal Growth Factor Receptor (EGFR) mutational assay using giant magnetoresistive (GMR) nanosensors. This assay was validated in 36 plasma samples of non-small cell lung cancer patients with known EGFR mutations. We assessed therapy response through follow-up blood draws, determined concordance between the GMR assay and radiographic response, and ascertained progression-free survival of patients.
RESULTS: The GMR assay achieved analytical sensitivities of 0.01% mutant allelic fraction. In clinical samples, the assay had 87.5% sensitivity (95% CI = 64.0-97.8%) for Exon19 deletion and 90% sensitivity (95% CI = 69.9-98.2%) for L858R mutation with 100% specificity; our assay detected T790M resistance with 96.3% specificity (95% CI = 81.7-99.8%) with 100% sensitivity. After 2 weeks of therapy, 10 patients showed disappearance of ctDNA by GMR (predicted responders), whereas 3 patients did not (predicted nonresponders). These predictions were 100% concordant with radiographic response. Kaplan-Meier analysis showed responders had significantly (P < 0.0001) longer PFS compared to nonresponders (N/A vs. 12 weeks, respectively).
CONCLUSIONS: The GMR assay has high diagnostic sensitivity and specificity and is well suited for detecting EGFR mutations at diagnosis and noninvasively monitoring treatment response at the point-of-care. © American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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Year:  2021        PMID: 33393992     DOI: 10.1093/clinchem/hvaa307

Source DB:  PubMed          Journal:  Clin Chem        ISSN: 0009-9147            Impact factor:   12.167


  4 in total

1.  A GMR-based assay for quantification of the human response to influenza.

Authors:  Neeraja Ravi; Sarah E Chang; Luis M Franco; Sandesh C S Nagamani; Purvesh Khatri; Paul J Utz; Shan X Wang
Journal:  Biosens Bioelectron       Date:  2022-02-17       Impact factor: 10.618

2.  One-Shot Full-Range Quantification of Multi-Biomarkers With Different Abundance by a Tandem Giant Magnetoresistance Assay.

Authors:  Fanda Meng; Lei Zhang; Jie Lian; Weisong Huo; Xizeng Shi; Yunhua Gao
Journal:  Front Chem       Date:  2022-05-19       Impact factor: 5.545

3.  Magnetic force microscopy of an operational spin nano-oscillator.

Authors:  Seyed Amir Hossein Banuazizi; Afshin Houshang; Ahmad A Awad; Javad Mohammadi; Johan Åkerman; Liubov M Belova
Journal:  Microsyst Nanoeng       Date:  2022-06-15       Impact factor: 8.006

Review 4.  Giant Magnetoresistance Biosensors for Food Safety Applications.

Authors:  Shuang Liang; Phanatchakorn Sutham; Kai Wu; Kumar Mallikarjunan; Jian-Ping Wang
Journal:  Sensors (Basel)       Date:  2022-07-28       Impact factor: 3.847

  4 in total

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