Circulating Tumor DNA Methylation Level Is a More Accurate Prognostic Biomarker in Colon Cancer

Accurate preoperative staging is important for predicting prognosis and determining appropriate preoperative treatment. We retrospectively examined the prognostic impact of preoperative staging based on sizes of metastatic lymph nodes (LNs) in pStage II/III sigmoid and rectosigmoid (RS) colon cancer. We investigated the correlation of sizes of metastatic LNs with levels of methylation of the SOX11 gene in circulating tumor DNA (ctDNA).

The subjects were 353 patients with sigmoid and RS colon cancer. Patients in which the preoperative stage diagnosis was the same as the postoperative pathological diagnosis were classified as Group E, and those in which the preoperative stage diagnosis was underestimated compared to the postoperative pathological diagnosis were classified as Group U. The ctDNA methylation levels of the SOX11 gene were assessed with the quantitative methylation-specific polymerase chain reaction.

pT3N+ patients had significant differences in recurrence-free survival (RFS) between Groups E and U (p=0.01). The Relative Methylation Values (RMVs) for the SOX11 gene in patients with a short diameter <4 mm were significantly lower than in patients with a short diameter ≥4 mm (p=0.03). pT3 pStage III patients in which the N factor was understaged in preoperative clinical diagnosis had a favorable RFS. Patients with a short LN diameter (≤4 mm) had lower RMVs in ctDNA and longer RFS.

The methylation level of the SOX11 gene in ctDNA predicts RFS and affords more accurate prognostication than radiological staging based on LN size in pStage II/III sigmoid and RS colon cancer. The present results suggest that the extent of methylation of the SOX11 gene in ctDNA can serve as a prognostic biomarker of RFS of patients with pStage II/III sigmoid and RS colon cancer.