Abstract
Genome-wide DNA hypomethylation is associated with a worse prognosis in early-stage colorectal cancer. To measure genome-wide DNA methylation levels, long interspersed nucleotide element (LINE-1) repeats are used as a surrogate marker. Cohort studies on the clinical impact of genome-wide DNA methylation level in patients with only early-stage colon cancer, are currently lacking. This study aimed to investigate the prognostic value of LINE-1 methylation in a stage II colon cancer cohort (n = 164). Manual needle microdissection of tumor areas was performed on formalin-fixed paraffin-embedded tumor tissue sections followed by DNA extraction. Bisulfite converted DNA was used to assess tumor LINE-1 methylation level by qPCR. Patients with LINE-1 hypomethylated tumors had a significantly worse overall survival compared to patients with a higher level of LINE-1 tumor DNA methylation (HR 1.68, 95% CI 1.03–2.75; p = 0.04). This effect was more prominent in patients aged over 65 years (HR 2.00, 95% CI 1.13–3.52; p = 0.02), although the test for age interaction was not significant. No significant effect on recurrence-free survival was observed. Based on these results, tumor LINE-1 hypomethylation is associated with a worse overall survival in stage II colon cancer. Whether the origin of this causation is cancer-specific or age-related can be debated.
Highlights
Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies across the world [1]
Relevant biomarkers can be found at different molecular levels, and the role of epigenetics in carcinogenesis has become a focus in cancer research during the past decade
This study aimed to investigate the role of tumor LINE-1 methylation level and its relation to clinical outcome in stage II colon cancer
Summary
Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies across the world [1]. Tumor LINE-1 hypomethylation in relation to clinical outcome in CRC was predominantly studied in cohorts consisting of both colon and rectal cancer. Since an age-related global hypomethylation has been observed in the colon [19,20], analyses stratified by age were performed in this study It is uncertain whether the proposed prognostic value of LINE-1 hypomethylation is altered by MSI [21,22]. For this reason, the MLH1 methylation status was determined, as MLH1 promoter methylation is the most frequently observed cause of MSI in sporadic colon tumors [23]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
