Genome-wide methylation profiling identifies a novel gene signature for patients with synchronous colorectal cancer

Background: There are no robust tools for the diagnosis of synchronous colorectal cancer (SyCRC). Herein, we developed the first methylation signature to identify and characterize patients with SyCRC.
Methods: For biomarker discovery, we analyzed the genome-wide methylation profiles of 16 SyCRC and 18 solitary colorectal cancer (SoCRC) specimens. We thereafter established a methylation signature risk-scoring model to identify SyCRC in an independent cohort of 38 SyCRC and 42 SoCRC patients. In addition, we evaluated the prognostic value of the identified methylation profile.
Results: We identified six differentially methylated CpG probes/sites that distinguished SyCRC from SoCRC. In the validation cohort, we developed a methylation panel that identified patients with SyCRC from not only larger tumor (AUC=0.91) but also the paired remaining tumor (AUC=0.93). Moreover, high risk scores of our panel were associated with the development of metachronous CRC among patients with SyCRC (AUC=0.87) and emerged as an independent predictor for relapse-free survival (hazard ratio=2.72; 95% CI=1.12–6.61). Furthermore, the risk stratification model which combined with clinical risk factors was a diagnostic predictor of recurrence (AUC=0.90).
Conclusions: Our novel six-gene methylation panel robustly identifies patients with SyCRC, which has the clinical potential to improve the diagnosis and management of patients with CRC.

This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use (https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms), but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1038/s41416-022-02033-9