Back to Search Start Over

Methylated Cell-Free DNA Sequencing (MeD-seq) of LpnPI Digested Fragments to Identify Early Progression in Metastatic Renal Cell Carcinoma Patients on Watchful Waiting

Authors :
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
Internal medicine
CCA - Cancer Treatment and quality of life
CCA - Imaging and biomarkers
Pathology
Medical Oncology
Developmental Biology
Guided Treatment in Optimal Selected Cancer Patients (GUTS)
Source :
Cancers, Volume 15, Issue 5, Pages: 1374, Cancers, 15, 5, Cancers, 15(5):1374. Multidisciplinary Digital Publishing Institute (MDPI), Bos, M K, Verhoeff, S R, Oosting, S F, Menke-van der Houven van Oordt, W C, Boers, R G, Boers, J B, Gribnau, J, Martens, J W M, Sleijfer, S, van Herpen, C M L & Wilting, S M 2023, ' 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, vol. 15, no. 5, 1374 . https://doi.org/10.3390/cancers15051374, Cancers, 15(5):1374. MDPI AG, Cancers, 15
Publication Year :
2023
Publisher :
Multidisciplinary Digital Publishing Institute, 2023.

Abstract

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, p = 0.018), but not a shorter WW-time (p = 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, p = 0.01), whereas only our RCC-specific methylation score (HR 4.45, p = 0.02) was significantly associated with PFS. The results of this study suggest that cfDNA methylation is predictive of PFS but not WW.

Details

Language :
English
ISSN :
20726694
Database :
OpenAIRE
Journal :
Cancers
Accession number :
edsair.doi.dedup.....7fccc792be5985f0cba5dab932188729
Full Text :
https://doi.org/10.3390/cancers15051374