Abstract
Background: I (the first author) studied DNA methylation in cancer at Johns Hopkins University from December 2013 to July 2016. In this review, we introduce our DNA methylation study in gastric cancer.
Across a diverse spectrum of solid malignancies, Checkpoint with Forkhead and Ring Finger Domains (CHFR) is most frequently inactivated by promoter CpG island methylation and has shown to be a marker of poor prognosis and increased sensitivity to treatment with taxanes. We retrospectively investigated CHFR promoter methylation in gastric cancer as a method for isolating those patients who would derive the most benefit from taxane-based regimens and as an indicator of prognosis.
Materials and Methods: One hundred thirty-six formalin-fixed paraffin-embedded (FFPE) primary tumor samples were collected from patients with gastric cancer who underwent surgery with curative intent at the Juntendo University Shizuoka Hospital between 2005 and 2012. We employed Quantitative Methylation-Specific PCR (qMSP) with bisulfite-modified DNA as a template for fluorescence-based real time PCR. We categorized patients into two groups: the low group (CHFR-relative methylation value (RMV) <10.3%) and the high group (CHFR-RMV ≥10.3%) based on Akaike’s information criteria (AIC).
Results: CHFR-RMVs in cancer tissues were significantly higher than those in normal-appearing adjacent non-cancerous tissues (p=0.0001). The cancer-specific survival among the patients in the high group was significantly worse than that among the patients in the low group (p=0.002).
Conclusions: CHFR promoter methylation is an independent prognostic marker of poor prognosis in gastric cancer.
© 2018 The Juntendo Medical Society. This is an open access article distributed under the terms of Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original source is properly credited.
