Molecular Alterations in Circulating Cell-Free DNA in Patients with Colorectal Adenoma or Carcinoma

Purpose: The aim of this study was to evaluate the clinical value of plasma cell-free DNA (cfDNA) in the diagnosis of colorectal cancer (CRC).

Patients and methods: The plasma cfDNA and tissue DNA mutation profiles were investigated in 77 patients (9 colon polyps, 18 colon adenoma, 26 colon cancer, and 24 rectal cancer) by a cancer gene-targeted NGS panel.

Results: During the progression from adenoma to carcinoma, mutations occur in genes such as RAS, Wnt, Hippo, Nrf2, TGFβ, PI3K, Notch, and P53, as well as in those encoding cell cycle pathway components. The somatic mutation burden and plasma cfDNA concentration were significantly higher in the colon carcinoma group than in the adenoma and colon polyp groups. The combination of plasma cfDNA concentration, CEA, and cfDNA had a significantly greater area under the curve than cfDNA or CEA alone. Right-sided colon cancer tissues showed a greater distribution of somatic mutations among more genes than left-sided colon cancer tissues. In addition, tissue tumor mutational burden (TMB) was higher in the right-sided colon cancer group than in the rectal cancer or left-sided colon cancer group (P<0.05).

Conclusion: These results may indicate that somatic mutations in plasma cfDNA are potential biomarkers for the diagnosis of CRC. In addition, somatic mutations may be distributed in more genes and pathways in right-sided colon cancer than in left-side colon cancer.