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Title |
Detection of KRAS G12/G13 Mutations in Cell Free-DNA by Droplet Digital PCR, Offers Prognostic Information for Patients with Advanced Non-Small Cell Lung Cancer |
Author
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Michaelidou, Kleita
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Author
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Koutoulaki, Chara
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Author
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Mavridis, Konstantinos
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Author
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Vorrias, Eleftherios
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Author
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Papadaki, Maria A.
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Author
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Koutsopoulos, Anastasios V.
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Author
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Mavroudis, Dimitrios
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Author
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Agelaki, Sofia
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Abstract |
KRAS mutations are found in approximately one third of non-small cell lung cancer (NSCLC) patients. In this study, we aim to investigate whether KRAS G12/G13 mutant allele fraction (MAF) in cell-free DNA (cfDNA) can provide meaningful prognostic information in NSCLC. Multiplex droplet-digital PCR was used to quantitatively assess KRAS G12/G13 MAF in cfDNA from 114 pre-treated advanced disease NSCLC patients. In 14 patients, changes in KRAS G12/G13 MAF were longitudinally monitored during treatment. Plasma KRAS G12/G13 status was associated with poor patients’ outcome in terms of progression-free survival (PFS) (p < 0.001) and overall survival (OS) (p < 0.001). In multivariate analysis, the detection of plasma KRAS mutations was an independent predictor of adverse PFS (HR = 3.12; p < 0.001) and OS (HR = 2.53; p = 0.002). KRAS G12/G13 MAF at first treatment evaluation (T1) was higher (p = 0.013) among patients experiencing progressive disease compared to those with disease control, and increased KRAS MAF at T1 was associated (p = 0.005) with shorter PFS. On the contrary, no association was observed between tissue KRAS mutation status and patients’ prognosis. Our results show that ddPCR-based detection of KRAS G12/G13 mutations in plasma could serve as an independent biomarker of unfavorable prognosis in NSCLC patients. Changes in KRAS MAF can provide valuable information for monitoring patient outcome during treatment.
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Language |
English |
Subject |
Liquid biopsy |
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Molecular testing |
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NSCLC |
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Prognostic biomarker |
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ctDNA |
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ddPCR |
Issue date |
2020-11-20 |
Collection
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School/Department--School of Medicine--Department of Medicine--Publications
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Type of Work--Publications
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Notes |
European Commission Horizon 2020-Research and Innovation Program H2020-FETOPEN-1-2016-2017 (GA NUMBER-737212-Capturing non-Amplified Tumor Circulating DNA with Ultrasound Hydrodynamics (CATCH-U-DNA)).
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Access Rights |
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Permanent Link |
https://elocus.lib.uoc.gr//dlib/9/6/6/metadata-dlib-1607326363-512654-19551.tkl
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Views |
1023 |