Methylated Cell-Free DNA Sequencing (MeD-seq) of LpnPI Digested Fragments to Identify Early Progression in Metastatic Renal Cell Carcinoma Patients on Watchful Waiting
According to the current guidelines, watchful waiting (WW) is a feasible option for patients with good or intermediate prognosis renal-cell carcinoma (RCC). However, some patients rapidly progress during WW, requiring the initiation of treatment. Here, we explore whether we can identify those patien...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/5/1374 |
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| author | Manouk K. Bos Sarah R. Verhoeff Sjoukje F. Oosting Willemien C. Menke-van der Houven van Oordt Ruben G. Boers Joachim B. Boers Joost Gribnau John W. M. Martens Stefan Sleijfer Carla M. L. van Herpen Saskia M. Wilting |
| author_facet | Manouk K. Bos Sarah R. Verhoeff Sjoukje F. Oosting Willemien C. Menke-van der Houven van Oordt Ruben G. Boers Joachim B. Boers Joost Gribnau John W. M. Martens Stefan Sleijfer Carla M. L. van Herpen Saskia M. Wilting |
| author_sort | Manouk K. Bos |
| collection | DOAJ |
| description | According to the current guidelines, watchful waiting (WW) is a feasible option for patients with good or intermediate prognosis renal-cell carcinoma (RCC). However, some patients rapidly progress during WW, requiring the initiation of treatment. Here, we explore whether we can identify those patients using circulating cell-free DNA (cfDNA) methylation. We first defined a panel of RCC-specific circulating methylation markers by intersecting differentially methylated regions from a publicly available dataset with known RCC methylation markers from the literature. The resulting RCC-specific methylation marker panel of 22 markers was subsequently evaluated for an association with rapid progression by methylated DNA sequencing (MeD-seq) in serum from 10 HBDs and 34 RCC patients with a good or intermediate prognosis starting WW in the IMPACT-RCC study. Patients with an elevated RCC-specific methylation score compared to HBDs had a shorter progression-free survival (PFS, <i>p</i> = 0.018), but not a shorter WW-time (<i>p</i> = 0.15). Cox proportional hazards regression showed that only the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria were significantly associated with WW time (HR 2.01, <i>p</i> = 0.01), whereas only our RCC-specific methylation score (HR 4.45, <i>p</i> = 0.02) was significantly associated with PFS. The results of this study suggest that cfDNA methylation is predictive of PFS but not WW. |
| first_indexed | 2024-03-11T07:30:08Z |
| format | Article |
| id | doaj.art-cbabc4b832614067b0099dc4352b4ac8 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T07:30:08Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-cbabc4b832614067b0099dc4352b4ac82023-11-17T07:23:17ZengMDPI AGCancers2072-66942023-02-01155137410.3390/cancers15051374Methylated Cell-Free DNA Sequencing (MeD-seq) of LpnPI Digested Fragments to Identify Early Progression in Metastatic Renal Cell Carcinoma Patients on Watchful WaitingManouk K. Bos0Sarah R. Verhoeff1Sjoukje F. Oosting2Willemien C. Menke-van der Houven van Oordt3Ruben G. Boers4Joachim B. Boers5Joost Gribnau6John W. M. Martens7Stefan Sleijfer8Carla M. L. van Herpen9Saskia M. Wilting10Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Medical Oncology, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsDepartment of Medical Oncology, University Medical Centre Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The NetherlandsDepartment of Developmental Biology, Erasmus Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Developmental Biology, Erasmus Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Developmental Biology, Erasmus Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Medical Oncology, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsDepartment of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD Rotterdam, The NetherlandsAccording to the current guidelines, watchful waiting (WW) is a feasible option for patients with good or intermediate prognosis renal-cell carcinoma (RCC). However, some patients rapidly progress during WW, requiring the initiation of treatment. Here, we explore whether we can identify those patients using circulating cell-free DNA (cfDNA) methylation. We first defined a panel of RCC-specific circulating methylation markers by intersecting differentially methylated regions from a publicly available dataset with known RCC methylation markers from the literature. The resulting RCC-specific methylation marker panel of 22 markers was subsequently evaluated for an association with rapid progression by methylated DNA sequencing (MeD-seq) in serum from 10 HBDs and 34 RCC patients with a good or intermediate prognosis starting WW in the IMPACT-RCC study. Patients with an elevated RCC-specific methylation score compared to HBDs had a shorter progression-free survival (PFS, <i>p</i> = 0.018), but not a shorter WW-time (<i>p</i> = 0.15). Cox proportional hazards regression showed that only the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria were significantly associated with WW time (HR 2.01, <i>p</i> = 0.01), whereas only our RCC-specific methylation score (HR 4.45, <i>p</i> = 0.02) was significantly associated with PFS. The results of this study suggest that cfDNA methylation is predictive of PFS but not WW.https://www.mdpi.com/2072-6694/15/5/1374metastatic renal cell carcinomawatchful waitingDNA methylationcfDNA |
| spellingShingle | Manouk K. Bos Sarah R. Verhoeff Sjoukje F. Oosting Willemien C. Menke-van der Houven van Oordt Ruben G. Boers Joachim B. Boers Joost Gribnau John W. M. Martens Stefan Sleijfer Carla M. L. van Herpen Saskia M. Wilting Methylated Cell-Free DNA Sequencing (MeD-seq) of LpnPI Digested Fragments to Identify Early Progression in Metastatic Renal Cell Carcinoma Patients on Watchful Waiting Cancers metastatic renal cell carcinoma watchful waiting DNA methylation cfDNA |
| title | Methylated Cell-Free DNA Sequencing (MeD-seq) of LpnPI Digested Fragments to Identify Early Progression in Metastatic Renal Cell Carcinoma Patients on Watchful Waiting |
| title_full | Methylated Cell-Free DNA Sequencing (MeD-seq) of LpnPI Digested Fragments to Identify Early Progression in Metastatic Renal Cell Carcinoma Patients on Watchful Waiting |
| title_fullStr | Methylated Cell-Free DNA Sequencing (MeD-seq) of LpnPI Digested Fragments to Identify Early Progression in Metastatic Renal Cell Carcinoma Patients on Watchful Waiting |
| title_full_unstemmed | Methylated Cell-Free DNA Sequencing (MeD-seq) of LpnPI Digested Fragments to Identify Early Progression in Metastatic Renal Cell Carcinoma Patients on Watchful Waiting |
| title_short | Methylated Cell-Free DNA Sequencing (MeD-seq) of LpnPI Digested Fragments to Identify Early Progression in Metastatic Renal Cell Carcinoma Patients on Watchful Waiting |
| title_sort | methylated cell free dna sequencing med seq of lpnpi digested fragments to identify early progression in metastatic renal cell carcinoma patients on watchful waiting |
| topic | metastatic renal cell carcinoma watchful waiting DNA methylation cfDNA |
| url | https://www.mdpi.com/2072-6694/15/5/1374 |
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