DNA methylation markers detected in blood, stool, urine, and tissue in colorectal cancer: a systematic review of paired
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REVIEW
DNA methylation markers detected in blood, stool, urine, and tissue in colorectal cancer: a systematic review of paired samples Eivor Alette Laugsand 1,2
&
Siv Sellæg Brenne 1,2 & Frank Skorpen 3
Accepted: 17 September 2020 # The Author(s) 2020
Abstract Purpose Methylated cell-free DNA in liquid biopsies are promising non-invasive biomarkers for colorectal cancer (CRC). Optimal markers would have high sensitivity and specificity for early detection of CRC and could be detected in more than one type of material from the patient. We systematically reviewed the literature on DNA methylation markers of colorectal cancer, detected in more than one type of material, regarding their potential as contributors to a panel for screening and follow-up of CRC. Methods The databases MEDLINE, Web of Science, and Embase were systematically searched. Data extraction and review was performed by two authors independently. Agreement between methylation status in tissue and other materials (blood/stool/urine) was analyzed using the McNemar test and Cohen’s kappa. Results From the 51 included studies, we identified seven single markers with sensitivity ≥ 75% and specificity ≥ 90% for CRC. We also identified one promising plasma panel and two stool panels. The correspondence of methylation status was evaluated as very good for four markers, but only marginal for most of the other markers was investigated (12 of 21). Conclusion The included studies reported only some of the variables and markers of interest and included few patients. Hence, a meta-analysis was not possible at this point. Larger, prospective studies must be designed to study the discordant detection of markers in tissue and liquid biopsies. When reporting their findings, such studies should use a standardized format. Keywords Colorectal cancer . Liquid biopsy . DNA methylation . cfDNA . Biomarker
Introduction Colorectal cancer (CRC) develops over years or decades through genetic and epigenetic alterations [1]. CRC is the Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00384-020-03757-x) contains supplementary material, which is available to authorized users. * Eivor Alette Laugsand [email protected] 1
Department of Surgery, Levanger Hospital, Nord-Trøndelag Hospital trust, N-7600 Levanger, Norway
2
Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway
3
Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway
second leading cause of cancer-related death in the Western world [2, 3], and its treatment and follow-up have a massive impact on the quality of life [4, 5]. Measures to increase CRC survival would be to diagnose the disease at an earlier stage, more reliably identify patients with residual disease after treatment, more accurately diagnose recurrence, and more closely monitor the
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