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

Area of Science:

• Oncology
• Molecular Diagnostics
• Cancer Genomics

Background:

• Accurate preoperative staging is crucial for predicting prognosis and guiding treatment in sigmoid and rectosigmoid (RS) colon cancer.
• Current radiological staging based on metastatic lymph node (LN) size has limitations in pStage II/III disease.

Purpose of the Study:

• To evaluate the prognostic impact of preoperative staging using metastatic LN size in pStage II/III sigmoid and RS colon cancer.
• To investigate the correlation between metastatic LN size and SOX11 gene methylation levels in circulating tumor DNA (ctDNA).

Main Methods:

• Retrospective analysis of 353 patients with sigmoid and RS colon cancer.
• Classification of patients into accurately staged (Group E) and understaged (Group U) groups based on preoperative vs. postoperative diagnosis.
• Quantitative assessment of SOX11 gene methylation in ctDNA using methylation-specific polymerase chain reaction.

Main Results:

• pT3N+ patients with understaged preoperative diagnosis (Group U) showed significant differences in recurrence-free survival (RFS) compared to accurately staged patients (Group E).
• Lower SOX11 gene methylation levels (Relative Methylation Values - RMVs) were observed in patients with smaller LN short diameters (<4 mm).
• Patients with smaller LNs (≤4 mm) exhibited lower ctDNA methylation levels and longer RFS.

Conclusions:

• SOX11 gene methylation in ctDNA serves as a more accurate prognostic biomarker for RFS than LN size-based radiological staging in pStage II/III sigmoid and RS colon cancer.
• The extent of SOX11 gene methylation in ctDNA can reliably predict RFS, improving prognostication for these patients.