Whole blood DNA methylation aging markers predict colorectal cancer survival: a prospective cohort study

Xin Gào*, Yan Zhang, Daniel Boakye, Xiangwei Li, Jenny Chang-Claude, Michael Hoffmeister, Hermann Brenner

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)
1 Downloads (Pure)

Abstract

Background
Blood DNA methylation-based aging algorithms predict mortality in the general population. We investigated the prognostic value of five established DNA methylation aging algorithms for patients with colorectal cancer (CRC).

Methods
AgeAccelHorvath, AgeAccelHannum, DNAmMRscore, AgeAccelPheno and AgeAccelGrim were constructed using whole blood epi-genomic data from 2206 CRC patients. After a median follow-up of 6.2 years, 1079 deaths were documented, including 596 from CRC. Associations of the aging algorithms with survival outcomes were evaluated using the Cox regression and survival curves. Harrell’s C-statistics were computed to investigate predictive performance.

Results
Adjusted hazard ratios (95% confidence intervals) of all-cause mortality for patients in the third compared to the first tertile were 1.66 (1.32, 2.09) for the DNAmMRscore, 1.35 (1.14, 1.59) for AgeAccelPheno and 1.65 (1.37, 2.00) for AgeAccelGrim, even after adjustment for age, sex and stage. AgeAccelHorvath and AgeAccelHannum were not associated with all-cause or CRC-specific mortality. In stage-specific analyses, associations were much stronger for patients with early or intermediate stage cancers (stages I, II and III) than for patients with metastatic (stage IV) cancers. Associations were weaker and less often statistically significant for CRC-specific mortality. Adding DNAmMRscore, AgeAccelPheno or AgeAccelGrim to models including age, sex and tumor stage improved predictive performance moderately.

Conclusions
DNAmMRscore, AgeAccelPheno and AgeAccelGrim could serve as non-invasive CRC prognostic biomarkers independent of other commonly used markers. Further research should aim for tailoring and refining such algorithms for CRC patients and to explore their value for enhanced prediction of treatment success and treatment decisions.
Original languageEnglish
Article number184
Number of pages13
JournalClinical Epigenetics
Volume12
DOIs
Publication statusPublished - 30 Nov 2020
Externally publishedYes

Keywords

  • DNA methylation
  • aging
  • whole blood
  • colorectal cancer
  • prognosis
  • mortality

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