Lessons from a systematic literature search on diagnostic DNA methylation biomarkers for colorectal cancer: how to increase research value and decrease research waste

Zheng Feng, Cary J G Oberije, Alouisa J P van de Wetering, Alexander Koch, Kim A D Wouters, Ad A M Masclee, Nathalie Vaes, Beatriz Carvalho, Gerrit A Meijer, Maurice P Zeegers, James G Herman, Veerle Melotte, Manon van Engeland, Kim M Smits*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

Abstract

ABSTRACT: BackgroundTo improve colorectal cancer (CRC) survival and lower incidence rates, colonoscopy and/or fecal immunochemical tests (FIT) screening is widely implemented. Although candidate DNA methylation biomarkers have been published to improve or complement FIT, clinical translation is limited. Here, we describe technical and methodological problems encountered after a systematic literature search and provide recommendations to increase (clinical) value and decrease research waste in biomarker research. Additionally, we present current evidence for diagnostic CRC DNA methylation biomarkers.MethodsA systematic literature search identified 331 diagnostic DNA methylation marker studies published before November 2020 in PubMed, Embase, Cochrane Library, or Google Scholar. For 136 bodily fluid studies, extended data extraction was performed. STARD criteria and level of evidence were registered to assess reporting quality and strength for clinical translation.ResultsOur systematic literature search revealed multiple issues, that hamper the development of DNA methylation biomarkers for CRC diagnosis, including methodological and technical heterogeneity, and lack of validation or clinical translation. For example, clinical translation and independent validation was limited, with 100/434 (23%) markers studied in bodily fluids, 3/434 (0.7%) translated into clinical tests, and independent validation for 92/411 (22%) tissue markers and 59/100 (59%) bodily fluids markers.DiscussionThis systematic literature search revealed that major requirements to develop clinically relevant diagnostic CRC DNA methylation markers are often lacking. To avoid the resulting research waste, clinical needs, intended biomarker use and independent validation should be better considered prior to study design. In addition, improved reporting quality would facilitate meta-analysis, thereby increasing level of evidence and enabling clinical translation.

Original languageEnglish
Article number00499
Number of pages10
JournalClinical and Translational Gastroenterology
Volume13
Issue number6
Early online date18 May 2022
DOIs
Publication statusPublished - 1 Jun 2022

Keywords

  • ACCURACY
  • BLOOD
  • COLONOSCOPY
  • FECAL IMMUNOCHEMICAL TEST
  • METAANALYSIS
  • PERFORMANCE
  • PRODUCTIVITY
  • SCREENING-PROGRAM
  • TESTS
  • TRENDS

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