DNA Methylation Analysis in Plasma Cell-Free DNA and Paired CTCs of NSCLC Patients before and after Osimertinib Treatment
Osimertinib has been an effective second-line treatment in EGFR mutant NSCLC patients; however, resistance inevitably occurs. DNA methylation has been previously implicated in NSCLC progression and often in therapy resistance, however its distinct role in osimertinib resistance is not elucidated as...
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MDPI AG
2021-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/23/5974 |
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| author | Aliki Ntzifa Dora Londra Theodoros Rampias Athanasios Kotsakis Vassilis Georgoulias Evi Lianidou |
| author_facet | Aliki Ntzifa Dora Londra Theodoros Rampias Athanasios Kotsakis Vassilis Georgoulias Evi Lianidou |
| author_sort | Aliki Ntzifa |
| collection | DOAJ |
| description | Osimertinib has been an effective second-line treatment in EGFR mutant NSCLC patients; however, resistance inevitably occurs. DNA methylation has been previously implicated in NSCLC progression and often in therapy resistance, however its distinct role in osimertinib resistance is not elucidated as yet. In the present study, we directly compared DNA methylation of nine selected genes (<i>RASSF1A</i>, <i>RASSF10</i>, <i>APC</i>, <i>WIF-1</i>, <i>BRMS1</i>, <i>SLFN11</i>, <i>RARβ</i>, <i>SHISA3</i>, and <i>FOXA1</i>) in plasma-cfDNA and paired CTCs of NSCLC patients who were longitudinally monitored during osimertinib treatment. Peripheral blood (PB) from 42 NSCLC patients was obtained at two time points: (a) baseline: before treatment with osimertinib and (b) at progression of disease (PD). DNA methylation of the selected genes was detected in plasma-cfDNA (<i>n</i> = 80) and in paired CTCs (<i>n</i> = 74). Direct comparison of DNA methylation of six genes between plasma-cfDNA and paired CTC samples (<i>n</i> = 70) revealed a low concordance, indicating that CTCs and cfDNA give complementary information. DNA methylation analysis of plasma-cfDNA and CTCs indicated that when at least one of these genes was methylated there was a statistically significant increase at PD compared to baseline (<i>p</i> = 0.031). For the first time, DNA methylation analysis in plasma-cfDNA and paired CTCs of NSCLC patients during osimertinib therapy indicated that DNA methylation of these genes could be a possible resistance mechanism. |
| first_indexed | 2024-03-10T04:55:52Z |
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| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T04:55:52Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-07c91abc66204024b546ce6b6ea6f8042023-11-23T02:12:26ZengMDPI AGCancers2072-66942021-11-011323597410.3390/cancers13235974DNA Methylation Analysis in Plasma Cell-Free DNA and Paired CTCs of NSCLC Patients before and after Osimertinib TreatmentAliki Ntzifa0Dora Londra1Theodoros Rampias2Athanasios Kotsakis3Vassilis Georgoulias4Evi Lianidou5Analysis of Circulating Tumor Cells Lab, Lab of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, GreeceAnalysis of Circulating Tumor Cells Lab, Lab of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, GreeceBasic Research Center, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, GreeceFaculty of Medicine, School of Health Sciences, University of Thessaly, 41110 Larissa, GreeceDepartment of Medical Oncology, Hellenic Oncology Research Group (HORG), 11471 Athens, GreeceAnalysis of Circulating Tumor Cells Lab, Lab of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, GreeceOsimertinib has been an effective second-line treatment in EGFR mutant NSCLC patients; however, resistance inevitably occurs. DNA methylation has been previously implicated in NSCLC progression and often in therapy resistance, however its distinct role in osimertinib resistance is not elucidated as yet. In the present study, we directly compared DNA methylation of nine selected genes (<i>RASSF1A</i>, <i>RASSF10</i>, <i>APC</i>, <i>WIF-1</i>, <i>BRMS1</i>, <i>SLFN11</i>, <i>RARβ</i>, <i>SHISA3</i>, and <i>FOXA1</i>) in plasma-cfDNA and paired CTCs of NSCLC patients who were longitudinally monitored during osimertinib treatment. Peripheral blood (PB) from 42 NSCLC patients was obtained at two time points: (a) baseline: before treatment with osimertinib and (b) at progression of disease (PD). DNA methylation of the selected genes was detected in plasma-cfDNA (<i>n</i> = 80) and in paired CTCs (<i>n</i> = 74). Direct comparison of DNA methylation of six genes between plasma-cfDNA and paired CTC samples (<i>n</i> = 70) revealed a low concordance, indicating that CTCs and cfDNA give complementary information. DNA methylation analysis of plasma-cfDNA and CTCs indicated that when at least one of these genes was methylated there was a statistically significant increase at PD compared to baseline (<i>p</i> = 0.031). For the first time, DNA methylation analysis in plasma-cfDNA and paired CTCs of NSCLC patients during osimertinib therapy indicated that DNA methylation of these genes could be a possible resistance mechanism.https://www.mdpi.com/2072-6694/13/23/5974DNA methylationliquid biopsycirculating tumor cellscell-free DNANSCLCosimertinib |
| spellingShingle | Aliki Ntzifa Dora Londra Theodoros Rampias Athanasios Kotsakis Vassilis Georgoulias Evi Lianidou DNA Methylation Analysis in Plasma Cell-Free DNA and Paired CTCs of NSCLC Patients before and after Osimertinib Treatment Cancers DNA methylation liquid biopsy circulating tumor cells cell-free DNA NSCLC osimertinib |
| title | DNA Methylation Analysis in Plasma Cell-Free DNA and Paired CTCs of NSCLC Patients before and after Osimertinib Treatment |
| title_full | DNA Methylation Analysis in Plasma Cell-Free DNA and Paired CTCs of NSCLC Patients before and after Osimertinib Treatment |
| title_fullStr | DNA Methylation Analysis in Plasma Cell-Free DNA and Paired CTCs of NSCLC Patients before and after Osimertinib Treatment |
| title_full_unstemmed | DNA Methylation Analysis in Plasma Cell-Free DNA and Paired CTCs of NSCLC Patients before and after Osimertinib Treatment |
| title_short | DNA Methylation Analysis in Plasma Cell-Free DNA and Paired CTCs of NSCLC Patients before and after Osimertinib Treatment |
| title_sort | dna methylation analysis in plasma cell free dna and paired ctcs of nsclc patients before and after osimertinib treatment |
| topic | DNA methylation liquid biopsy circulating tumor cells cell-free DNA NSCLC osimertinib |
| url | https://www.mdpi.com/2072-6694/13/23/5974 |
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