Conclusions
In conclusion, the findings in this study support the theory that buffy coat-derived DNA methylation markers could be used to identify biomarkers among cirrhosis patients at high risk for HCC before clinical symptoms appear. A further study with a large prospective cohort is required to validate these findings.
Methods
We performed genome-wide DNA methylation profiling using Illumina Infinium MethylationEPI BeadChip in pre-diagnostic samples from 22 cirrhosis patients who subsequently developed HCC and 22 cirrhosis patients who remained HCC-free during an average 4-year follow-up. In a secondary analysis, we examined a subset of patients without hepatitis C virus (HCV) infection.
Results
We identified three differentially methylated positions (DMPs) located in ADAM12 (cg13674437) and PSD3 (cg06758847 and cg24595678) that show a strong association with HCC risk (lower median vs. higher median hazards ratio (HR): HR cg13674437 = 0.34, 95% CI = 0.14-0.83; HR cg06758847 = 4.89, 95% CI = 1.79-13.33; HR cg24595678 = 11.19, 95% CI = 3.27-38.35). After excluding all HCV-active patients from our analysis, the HR for the DMPs remained significant. Conclusions: In