Detection of colorectal cancer in urine using DNA methylation analysis

Bach, Sander; Paulis, I.; Sluiter, Nina R.; Tibbesma, Marco; Martin, Ivonne; Wiel, Mark A. van de; Tuynman, Jurriaan B.; Bahce, Idris; Kazemier, Geert; Steenbergen, Renske D.M.

doi:10.1038/s41598-021-81900-6

“…Previous studies also did not find a day-to-day variation of cfDNA in plasma [22,24,40], in line with the current findings. The only patient characteristic that influenced urinary cfDNA concentration levels in this study was sex, with a significantly higher concentration found in females, following previous studies [41][42][43].…”

Section: Discussionsupporting

confidence: 84%

Dynamics of methylated cell-free DNA in the urine of non-small cell lung cancer patients

Bach

¹

,

Wever

²

,

Wiel

³

et al. 2021

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High levels of methylated DNA in urine represent an emerging biomarker for non-small cell lung cancer (NSCLC) detection and are the subject of ongoing research. This study aimed to investigate the circadian variation of urinary cell-free DNA (cfDNA) abundance and methylation levels of cancer-associated genes in NSCLC patients. In this prospective study of 23 metastatic NSCLC patients with active disease, patients were asked to collect six urine samples during the morning, afternoon, and evening of two subsequent days. Urinary cfDNA concentrations and methylation levels of CDO1, SOX17, and TAC1 were measured at each time point. Circadian variation and between-and within-subject variability were assessed using linear mixed models. Variability was estimated using the Intraclass Correlation Coefficient (ICC), representing reproducibility. No clear circadian patterns could be recognized for cfDNA concentrations or methylation levels across the different sampling time points. Significantly lower cfDNA concentrations were found in males (p=0.034). For cfDNA levels, the between-and within-subject variability were comparable, rendering an ICC of 0.49. For the methylation markers, ICCs varied considerably, ranging from 0.14 to 0.74. Test reproducibility could be improved by collecting multiple samples per patient. In conclusion, there is no preferred collection time for NSCLC detection in urine using methylation markers, but single measurements should be interpreted carefully, and serial sampling may increase test performance. This study contributes to the limited understanding of cfDNA dynamics in urine and the continued interest in urine-based liquid biopsies for cancer diagnostics.

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“…Colorectal cancer (CRC) is one of the most common malignant cancers and the second leading cause of cancer-related death worldwide [ 1 ]. Nutritional oxidative stress and inflammation of the colonic mucosa play an essential role in the molecular mechanism of CRC [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Improvement in Redox Homeostasis after Cytoreductive Surgery in Colorectal Adenocarcinoma

Salehi

¹

,

Mirmiranpour

²

,

Rabizadeh

³

et al. 2021

Oxidative Medicine and Cellular Longevity

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Colorectal cancer (CRC) as one the most common cancer type is associated with oxidative stress. Surgery is the only curative modality for early-stage CRC. The aim of this study was to evaluate the oxidative damage biomarkers as well as enzymatic and nonenzymatic antioxidants in patients with CRC before and after tumor resection and in healthy controls. 60 patients with stage I/II colorectal adenocarcinoma and 43 healthy controls were recruited in this study. We measured plasma levels of oxidative damage biomarkers, including advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), malondialdehyde (MDA), and oxidized low-density lipoprotein (ox-LDL) at baseline and after tumor removal. We also evaluated the plasma activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) as enzymatic antioxidants and the ferric reducing antioxidant power (FRAP) assay for nonenzymatic antioxidant capacity. Patients with CRC had significantly higher AGE, AOPP, MDA, and ox-LDL and also FRAP levels and higher SOD and GPx and lower CAT activity levels compared to healthy controls ( p < 0.05 ). We did not observe any statistically significant correlation between redox biomarkers and the size and stage of the tumor. AGEs ( 72.49 ± 4.7 vs. 67.93 ± 8.8 , p < 0.001 ), AOPP ( 137.64 ± 21.9 vs. 119.08 ± 33.1 , p < 0.001 ), MDA ( 3.56 ± 0.30 vs. 3.05 ± 0.33 , p < 0.001 ), and ox-LDL ( 19.78 ± 0.97 vs. 16.94 ± 1.02 , p < 0.001 ) concentrations reduced significantly after tumor removal. The largest effect sizes were found in ox-LDL ( d = − 2.853 , 95% CI 2.50-3.19) and MDA ( d = − 1.617 , 95% CI 0.43-0.57). Serum FRAP levels ( 1097.5 ± 156.7 vs. 1239.3 ± 290 , p < 0.001 ) and CAT ( 2.34 ± 0.34 vs. 2.63 ± 0.38 , p < 0.001 ), GPx ( 102.37 ± 6.58 vs. 108.03 ± 6.95 , p < 0.001 ), and SOD ( 5.13 ± 0.39 vs. 5.53 ± 0.31 , p < 0.001 ) activity levels increased significantly after surgery. The largest effect sizes among antioxidants were seen in SOD ( d = 1.135 , 95% CI 0.46-0.34) and GPx ( d = 0.836 , 95% CI 0.35-0.23). This study indicated that patients with colorectal cancer had higher levels of oxidative stress and antioxidant activity compared to healthy controls. After surgical resection of tumor, we observed a substantial improvement in redox homeostasis.

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“…DNA methylation marks have been detected in urine sediment in various cancer types such as bladder cancer [ 94 ], endometrial cancer [ 95 ], and prostate cancer [ 96 ]. Additionally, urinary cfDNA equally offers the opportunity for DNA methylation analysis in colorectal cancer [ 97 ], bladder cancer [ 98 ], and RCC [ 34 ].…”

Section: Epigenomic Modifications Of Cfdnamentioning

confidence: 99%

Liquid Biopsies beyond Mutation Calling: Genomic and Epigenomic Features of Cell-Free DNA in Cancer

Angeles

¹

,

Janke

²

,

Bauer

³

et al. 2021

Cancers

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Cell-free DNA (cfDNA) analysis using liquid biopsies is a non-invasive method to gain insights into the biology, therapy response, mechanisms of acquired resistance and therapy escape of various tumors. While it is well established that individual cancer treatment options can be adjusted by panel next-generation sequencing (NGS)-based evaluation of driver mutations in cfDNA, emerging research additionally explores the value of deep characterization of tumor cfDNA genomics and fragmentomics as well as nucleosome modifications (chromatin structure), and methylation patterns (epigenomics) for comprehensive and multi-modal assessment of cfDNA. These tools have the potential to improve disease monitoring, increase the sensitivity of minimal residual disease identification, and detection of cancers at earlier stages. Recent progress in emerging technologies of cfDNA analysis is summarized, the added potential clinical value is highlighted, strengths and limitations are identified and compared with conventional targeted NGS analysis, and current challenges and future directions are discussed.

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Detection of colorectal cancer in urine using DNA methylation analysis

Cited by 35 publications

References 47 publications

Dynamics of methylated cell-free DNA in the urine of non-small cell lung cancer patients

Dynamics of methylated cell-free DNA in the urine of non-small cell lung cancer patients

Improvement in Redox Homeostasis after Cytoreductive Surgery in Colorectal Adenocarcinoma

Liquid Biopsies beyond Mutation Calling: Genomic and Epigenomic Features of Cell-Free DNA in Cancer

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