Liquid Biopsy for Disease Monitoring in Non-Small Cell Lung Cancer: The Link between Biology and the Clinic
Introduction: Cell-free DNA (cfDNA) analysis offers a non-invasive method to identify sensitising and resistance mutations in advanced Non-Small Cell Lung Cancer (NSCLC) patients. Next-generation sequencing (NGS) of circulating free DNA (cfDNA) is a valuable tool for mutations detection and disease′...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-07-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/10/8/1912 |
| _version_ | 1827685672868118528 |
|---|---|
| author | Maria Gabriela O. Fernandes Catarina Sousa Joana Pereira Reis Natália Cruz-Martins Conceição Souto Moura Susana Guimarães Ana Justino Maria João Pina Adriana Magalhães Henrique Queiroga José Agostinho Marques José Carlos Machado José Luís Costa Venceslau Hespanhol |
| author_facet | Maria Gabriela O. Fernandes Catarina Sousa Joana Pereira Reis Natália Cruz-Martins Conceição Souto Moura Susana Guimarães Ana Justino Maria João Pina Adriana Magalhães Henrique Queiroga José Agostinho Marques José Carlos Machado José Luís Costa Venceslau Hespanhol |
| author_sort | Maria Gabriela O. Fernandes |
| collection | DOAJ |
| description | Introduction: Cell-free DNA (cfDNA) analysis offers a non-invasive method to identify sensitising and resistance mutations in advanced Non-Small Cell Lung Cancer (NSCLC) patients. Next-generation sequencing (NGS) of circulating free DNA (cfDNA) is a valuable tool for mutations detection and disease′s clonal monitoring. Material and methods: An amplicon-based targeted gene NGS panel was used to analyse 101 plasma samples of advanced non-small cell lung cancer (NSCLC) patients with known oncogenic mutations, mostly EGFR mutations, serially collected at different clinically relevant time points of the disease. Results: The variant allelic frequency (VAF) monitoring in consecutive plasma samples demonstrated different molecular response and progression patterns. The decrease in or the clearance of the mutant alleles was associated with response and the increase in or the emergence of novel alterations with progression. At the best response, the median VAF was 0% (0.0% to 3.62%), lower than that at baseline, with a median of 0.53% (0.0% to 9.9%) (<i>p</i> = 0.004). At progression, the VAF was significantly higher (median 4.67; range: 0.0–36.9%) than that observed at the best response (<i>p</i> = 0.001) and baseline (<i>p</i> = 0.006). These variations anticipated radiographic changes in most cases, with a median time of 0.86 months. Overall, the VAF evolution of different oncogenic mutations predicts clinical outcomes. Conclusion: The targeted NGS of circulating tumour DNA (ctDNA) has clinical utility to monitor treatment response in patients with advanced lung adenocarcinoma. |
| first_indexed | 2024-03-10T08:55:54Z |
| format | Article |
| id | doaj.art-cb45f69c6b824d58a00d44bd18661267 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T08:55:54Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-cb45f69c6b824d58a00d44bd186612672023-11-22T07:09:04ZengMDPI AGCells2073-44092021-07-01108191210.3390/cells10081912Liquid Biopsy for Disease Monitoring in Non-Small Cell Lung Cancer: The Link between Biology and the ClinicMaria Gabriela O. Fernandes0Catarina Sousa1Joana Pereira Reis2Natália Cruz-Martins3Conceição Souto Moura4Susana Guimarães5Ana Justino6Maria João Pina7Adriana Magalhães8Henrique Queiroga9José Agostinho Marques10José Carlos Machado11José Luís Costa12Venceslau Hespanhol13Pulmonology Department, Centro Hospitalar Universitário de São João, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, PortugalPulmonology Department, Centro Hospitalar Universitário de São João, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, PortugalFaculty of Medicine, University of Porto, Alameda Prof. Hernani Monteiro, 4200-319 Porto, PortugalPathology Department, Centro Hospitalar Universitário de São João, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, PortugalFaculty of Medicine, University of Porto, Alameda Prof. Hernani Monteiro, 4200-319 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, PortugalInstitute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, PortugalPulmonology Department, Centro Hospitalar Universitário de São João, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, PortugalPulmonology Department, Centro Hospitalar Universitário de São João, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, PortugalPulmonology Department, Centro Hospitalar Universitário de São João, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, PortugalFaculty of Medicine, University of Porto, Alameda Prof. Hernani Monteiro, 4200-319 Porto, PortugalFaculty of Medicine, University of Porto, Alameda Prof. Hernani Monteiro, 4200-319 Porto, PortugalPulmonology Department, Centro Hospitalar Universitário de São João, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, PortugalIntroduction: Cell-free DNA (cfDNA) analysis offers a non-invasive method to identify sensitising and resistance mutations in advanced Non-Small Cell Lung Cancer (NSCLC) patients. Next-generation sequencing (NGS) of circulating free DNA (cfDNA) is a valuable tool for mutations detection and disease′s clonal monitoring. Material and methods: An amplicon-based targeted gene NGS panel was used to analyse 101 plasma samples of advanced non-small cell lung cancer (NSCLC) patients with known oncogenic mutations, mostly EGFR mutations, serially collected at different clinically relevant time points of the disease. Results: The variant allelic frequency (VAF) monitoring in consecutive plasma samples demonstrated different molecular response and progression patterns. The decrease in or the clearance of the mutant alleles was associated with response and the increase in or the emergence of novel alterations with progression. At the best response, the median VAF was 0% (0.0% to 3.62%), lower than that at baseline, with a median of 0.53% (0.0% to 9.9%) (<i>p</i> = 0.004). At progression, the VAF was significantly higher (median 4.67; range: 0.0–36.9%) than that observed at the best response (<i>p</i> = 0.001) and baseline (<i>p</i> = 0.006). These variations anticipated radiographic changes in most cases, with a median time of 0.86 months. Overall, the VAF evolution of different oncogenic mutations predicts clinical outcomes. Conclusion: The targeted NGS of circulating tumour DNA (ctDNA) has clinical utility to monitor treatment response in patients with advanced lung adenocarcinoma.https://www.mdpi.com/2073-4409/10/8/1912lung canceradenocarcinomaliquid biopsycell-free DNAtumour-free DNAnext-generation sequencing |
| spellingShingle | Maria Gabriela O. Fernandes Catarina Sousa Joana Pereira Reis Natália Cruz-Martins Conceição Souto Moura Susana Guimarães Ana Justino Maria João Pina Adriana Magalhães Henrique Queiroga José Agostinho Marques José Carlos Machado José Luís Costa Venceslau Hespanhol Liquid Biopsy for Disease Monitoring in Non-Small Cell Lung Cancer: The Link between Biology and the Clinic Cells lung cancer adenocarcinoma liquid biopsy cell-free DNA tumour-free DNA next-generation sequencing |
| title | Liquid Biopsy for Disease Monitoring in Non-Small Cell Lung Cancer: The Link between Biology and the Clinic |
| title_full | Liquid Biopsy for Disease Monitoring in Non-Small Cell Lung Cancer: The Link between Biology and the Clinic |
| title_fullStr | Liquid Biopsy for Disease Monitoring in Non-Small Cell Lung Cancer: The Link between Biology and the Clinic |
| title_full_unstemmed | Liquid Biopsy for Disease Monitoring in Non-Small Cell Lung Cancer: The Link between Biology and the Clinic |
| title_short | Liquid Biopsy for Disease Monitoring in Non-Small Cell Lung Cancer: The Link between Biology and the Clinic |
| title_sort | liquid biopsy for disease monitoring in non small cell lung cancer the link between biology and the clinic |
| topic | lung cancer adenocarcinoma liquid biopsy cell-free DNA tumour-free DNA next-generation sequencing |
| url | https://www.mdpi.com/2073-4409/10/8/1912 |
| work_keys_str_mv | AT mariagabrielaofernandes liquidbiopsyfordiseasemonitoringinnonsmallcelllungcancerthelinkbetweenbiologyandtheclinic AT catarinasousa liquidbiopsyfordiseasemonitoringinnonsmallcelllungcancerthelinkbetweenbiologyandtheclinic AT joanapereirareis liquidbiopsyfordiseasemonitoringinnonsmallcelllungcancerthelinkbetweenbiologyandtheclinic AT nataliacruzmartins liquidbiopsyfordiseasemonitoringinnonsmallcelllungcancerthelinkbetweenbiologyandtheclinic AT conceicaosoutomoura liquidbiopsyfordiseasemonitoringinnonsmallcelllungcancerthelinkbetweenbiologyandtheclinic AT susanaguimaraes liquidbiopsyfordiseasemonitoringinnonsmallcelllungcancerthelinkbetweenbiologyandtheclinic AT anajustino liquidbiopsyfordiseasemonitoringinnonsmallcelllungcancerthelinkbetweenbiologyandtheclinic AT mariajoaopina liquidbiopsyfordiseasemonitoringinnonsmallcelllungcancerthelinkbetweenbiologyandtheclinic AT adrianamagalhaes liquidbiopsyfordiseasemonitoringinnonsmallcelllungcancerthelinkbetweenbiologyandtheclinic AT henriquequeiroga liquidbiopsyfordiseasemonitoringinnonsmallcelllungcancerthelinkbetweenbiologyandtheclinic AT joseagostinhomarques liquidbiopsyfordiseasemonitoringinnonsmallcelllungcancerthelinkbetweenbiologyandtheclinic AT josecarlosmachado liquidbiopsyfordiseasemonitoringinnonsmallcelllungcancerthelinkbetweenbiologyandtheclinic AT joseluiscosta liquidbiopsyfordiseasemonitoringinnonsmallcelllungcancerthelinkbetweenbiologyandtheclinic AT venceslauhespanhol liquidbiopsyfordiseasemonitoringinnonsmallcelllungcancerthelinkbetweenbiologyandtheclinic |