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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

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 wa...

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Autores principales: Michaelidou, Kleita, Koutoulaki, Chara, Mavridis, Konstantinos, Vorrias, Eleftherios, Papadaki, Maria A., Koutsopoulos, Anastasios V., Mavroudis, Dimitrios, Agelaki, Sofia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699710/
https://www.ncbi.nlm.nih.gov/pubmed/33233668
http://dx.doi.org/10.3390/cells9112514
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author Michaelidou, Kleita
Koutoulaki, Chara
Mavridis, Konstantinos
Vorrias, Eleftherios
Papadaki, Maria A.
Koutsopoulos, Anastasios V.
Mavroudis, Dimitrios
Agelaki, Sofia
author_facet Michaelidou, Kleita
Koutoulaki, Chara
Mavridis, Konstantinos
Vorrias, Eleftherios
Papadaki, Maria A.
Koutsopoulos, Anastasios V.
Mavroudis, Dimitrios
Agelaki, Sofia
author_sort Michaelidou, Kleita
collection PubMed
description 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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spelling pubmed-76997102020-11-29 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 Michaelidou, Kleita Koutoulaki, Chara Mavridis, Konstantinos Vorrias, Eleftherios Papadaki, Maria A. Koutsopoulos, Anastasios V. Mavroudis, Dimitrios Agelaki, Sofia Cells Article 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. MDPI 2020-11-20 /pmc/articles/PMC7699710/ /pubmed/33233668 http://dx.doi.org/10.3390/cells9112514 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Michaelidou, Kleita
Koutoulaki, Chara
Mavridis, Konstantinos
Vorrias, Eleftherios
Papadaki, Maria A.
Koutsopoulos, Anastasios V.
Mavroudis, Dimitrios
Agelaki, Sofia
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
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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699710/
https://www.ncbi.nlm.nih.gov/pubmed/33233668
http://dx.doi.org/10.3390/cells9112514
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