CpG-biomarkers in tumor tissue and prediction models for the survival of colorectal cancer: A systematic review and external validation study

Research output: Contribution to journalReview articleContributedpeer-review

Contributors

  • Tanwei Yuan - , German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Dominic Edelmann - , German Cancer Research Center (DKFZ) (Author)
  • Jakob N. Kather - , Else Kröner Fresenius Center for Digital Health, University Hospital Heidelberg (Author)
  • Ziwen Fan - , German Cancer Research Center (DKFZ) (Author)
  • Katrin E. Tagscherer - , Heidelberg University , University Medical Center Mainz (Author)
  • Wilfried Roth - , Heidelberg University , University Medical Center Mainz (Author)
  • Melanie Bewerunge-Hudler - , German Cancer Research Center (DKFZ) (Author)
  • Alexander Brobeil - , Heidelberg University  (Author)
  • Matthias Kloor - , Heidelberg University  (Author)
  • Hendrik Bläker - , Leipzig University (Author)
  • Barbara Burwinkel - , German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Hermann Brenner - , German Cancer Research Center (DKFZ) (Author)
  • Michael Hoffmeister - , German Cancer Research Center (DKFZ) (Author)

Abstract

The research aimed to identify previously published CpG-methylation-based prognostic biomarkers and prediction models for colorectal cancer (CRC) prognosis and validate them in a large external cohort. A systematic search was conducted, analyzing 298 unique CpGs and 12 CpG-based prognostic models from 28 studies. After adjustment for clinical variables, 48 CpGs and five prognostic models were confirmed to be associated with survival. However, the discrimination ability of the models was insufficient, with area under the receiver operating characteristic curves ranging from 0.53 to 0.62. Calibration accuracy was mostly poor, and no significant added prognostic value beyond traditional clinical variables was observed. All prognostic models were rated at high risk of bias. While a fraction of CpGs showed potential clinical utility and generalizability, the CpG-based prognostic models performed poorly and lacked clinical relevance.

Details

Original languageEnglish
Article number104199
JournalCritical Reviews in Oncology/Hematology
Volume193
Publication statusPublished - Jan 2024
Peer-reviewedYes

External IDs

PubMed 37952858

Keywords

Sustainable Development Goals

Keywords

  • Biomarkers, Colorectal cancer, DNA methylation, External validation, Prognosis, Colorectal Neoplasms/diagnosis, DNA Methylation, Humans, Biomarkers, Tumor