Detection of <i>KRAS</i> G12/G13 Mutations in Cell Free-DNA by Droplet Digital PCR, Offers Prognostic Information for Patients with Advanced Non-Small Cell Lung Cancer
<i>KRAS</i> mutations are found in approximately one third of non-small cell lung cancer (NSCLC) patients. In this study, we aim to investigate whether <i>KRAS</i> G12/G13 mutant allele fraction (MAF) in cell-free DNA (cfDNA) can provide meaningful prognostic information in N...
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MDPI AG
2020-11-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/11/2514 |
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| author | Kleita Michaelidou Chara Koutoulaki Konstantinos Mavridis Eleftherios Vorrias Maria A. Papadaki Anastasios V. Koutsopoulos Dimitrios Mavroudis Sofia Agelaki |
| author_facet | Kleita Michaelidou Chara Koutoulaki Konstantinos Mavridis Eleftherios Vorrias Maria A. Papadaki Anastasios V. Koutsopoulos Dimitrios Mavroudis Sofia Agelaki |
| author_sort | Kleita Michaelidou |
| collection | DOAJ |
| description | <i>KRAS</i> mutations are found in approximately one third of non-small cell lung cancer (NSCLC) patients. In this study, we aim to investigate whether <i>KRAS</i> 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 <i>KRAS</i> G12/G13 MAF in cfDNA from 114 pre-treated advanced disease NSCLC patients. In 14 patients, changes in <i>KRAS</i> G12/G13 MAF were longitudinally monitored during treatment. Plasma <i>KRAS</i> G12/G13 status was associated with poor patients’ outcome in terms of progression-free survival (PFS) (<i>p</i> < 0.001) and overall survival (OS) (<i>p</i> < 0.001). In multivariate analysis, the detection of plasma <i>KRAS</i> mutations was an independent predictor of adverse PFS (HR = 3.12; <i>p</i> < 0.001) and OS (HR = 2.53; <i>p</i> = 0.002). <i>KRAS</i> G12/G13 MAF at first treatment evaluation (T1) was higher (<i>p</i> = 0.013) among patients experiencing progressive disease compared to those with disease control, and increased <i>KRAS</i> MAF at T1 was associated (<i>p</i> = 0.005) with shorter PFS. On the contrary, no association was observed between tissue <i>KRAS</i> mutation status and patients’ prognosis. Our results show that ddPCR-based detection of <i>KRAS</i> G12/G13 mutations in plasma could serve as an independent biomarker of unfavorable prognosis in NSCLC patients. Changes in <i>KRAS</i> MAF can provide valuable information for monitoring patient outcome during treatment. |
| first_indexed | 2024-03-10T14:41:34Z |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T14:41:34Z |
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| spelling | doaj.art-03e5afb9950b49d5af7679b87c04674f2023-11-20T21:42:51ZengMDPI AGCells2073-44092020-11-01911251410.3390/cells9112514Detection of <i>KRAS</i> G12/G13 Mutations in Cell Free-DNA by Droplet Digital PCR, Offers Prognostic Information for Patients with Advanced Non-Small Cell Lung CancerKleita Michaelidou0Chara Koutoulaki1Konstantinos Mavridis2Eleftherios Vorrias3Maria A. Papadaki4Anastasios V. Koutsopoulos5Dimitrios Mavroudis6Sofia Agelaki7Laboratory of Translational Oncology, School of Medicine, University of Crete, 71110 Heraklion, Crete, GreeceLaboratory of Translational Oncology, School of Medicine, University of Crete, 71110 Heraklion, Crete, GreeceInstitute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, 70013 Heraklion, Crete, GreeceDepartment of Medical Oncology, University General Hospital of Heraklion, 71110 Heraklion, Crete, GreeceLaboratory of Translational Oncology, School of Medicine, University of Crete, 71110 Heraklion, Crete, GreeceDepartment of Pathology, University General Hospital of Heraklion, University of Crete, Medical School, 71110 Heraklion, Crete, GreeceLaboratory of Translational Oncology, School of Medicine, University of Crete, 71110 Heraklion, Crete, GreeceLaboratory of Translational Oncology, School of Medicine, University of Crete, 71110 Heraklion, Crete, Greece<i>KRAS</i> mutations are found in approximately one third of non-small cell lung cancer (NSCLC) patients. In this study, we aim to investigate whether <i>KRAS</i> 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 <i>KRAS</i> G12/G13 MAF in cfDNA from 114 pre-treated advanced disease NSCLC patients. In 14 patients, changes in <i>KRAS</i> G12/G13 MAF were longitudinally monitored during treatment. Plasma <i>KRAS</i> G12/G13 status was associated with poor patients’ outcome in terms of progression-free survival (PFS) (<i>p</i> < 0.001) and overall survival (OS) (<i>p</i> < 0.001). In multivariate analysis, the detection of plasma <i>KRAS</i> mutations was an independent predictor of adverse PFS (HR = 3.12; <i>p</i> < 0.001) and OS (HR = 2.53; <i>p</i> = 0.002). <i>KRAS</i> G12/G13 MAF at first treatment evaluation (T1) was higher (<i>p</i> = 0.013) among patients experiencing progressive disease compared to those with disease control, and increased <i>KRAS</i> MAF at T1 was associated (<i>p</i> = 0.005) with shorter PFS. On the contrary, no association was observed between tissue <i>KRAS</i> mutation status and patients’ prognosis. Our results show that ddPCR-based detection of <i>KRAS</i> G12/G13 mutations in plasma could serve as an independent biomarker of unfavorable prognosis in NSCLC patients. Changes in <i>KRAS</i> MAF can provide valuable information for monitoring patient outcome during treatment.https://www.mdpi.com/2073-4409/9/11/2514ctDNANSCLCddPCRliquid biopsyprognostic biomarkermolecular testing |
| spellingShingle | Kleita Michaelidou Chara Koutoulaki Konstantinos Mavridis Eleftherios Vorrias Maria A. Papadaki Anastasios V. Koutsopoulos Dimitrios Mavroudis Sofia Agelaki Detection of <i>KRAS</i> G12/G13 Mutations in Cell Free-DNA by Droplet Digital PCR, Offers Prognostic Information for Patients with Advanced Non-Small Cell Lung Cancer Cells ctDNA NSCLC ddPCR liquid biopsy prognostic biomarker molecular testing |
| title | Detection of <i>KRAS</i> 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 <i>KRAS</i> 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 <i>KRAS</i> 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 <i>KRAS</i> 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 <i>KRAS</i> 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 i kras i g12 g13 mutations in cell free dna by droplet digital pcr offers prognostic information for patients with advanced non small cell lung cancer |
| topic | ctDNA NSCLC ddPCR liquid biopsy prognostic biomarker molecular testing |
| url | https://www.mdpi.com/2073-4409/9/11/2514 |
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