Circulating Cell-Free DNA Levels Could Predict Oncological Outcomes of Patients Undergoing Esophagectomy for Esophageal Squamous Cell Carcinoma

Abstract

Circulating cell-free DNA (cfDNA) is a potential biomarker for cancer progression but its role is unclear in patients with esophageal squamous cell carcinoma (ESCC) after esophagectomy. We investigated relationships between plasma cfDNA levels and clinicopathological parameters in ESCC patients. Eighty-one ESCC patients who received esophagectomy were enrolled. Plasma samples from these patients and 95 normal controls were collected. DNA copy numbers were measured by real-time quantitative PCR. Subjects were divided into two groups by cfDNA level. Clinicopathological data were collected retrospectively and relationships between cfDNA levels and clinical parameters were evaluated. The cfDNA level in normal controls ranged from 0-4157 copies/mL. The cfDNA level of 96.3% ESCC patients was higher than the cutoff value (2447.26 copies/mL) with a specificity of 94.1%. The mean cfDNA concentration was 5918 copies/mL in lower and 53,311 copies/mL in higher cfDNA groups. No correlations were found between clinicopathological factors and cfDNA levels except for lymphovascular invasion. Higher cfDNA levels were associated with tumor relapse (p = 0.018). Five-year disease-free survival (DFS) and overall survival (OS) rates were 34.7% and 33.8%, respectively. Patients with higher cfDNA levels had poorer DFS (p = 0.013). Patients with higher cfDNA levels had poorer OS, but not significantly (p = 0.164). Circulating cfDNA could be a biomarker for tumor relapse of ESCC with high sensitivity and specificity. Higher cfDNA levels were associated with tumor relapse and shorter DFS after esophagectomy in ESCC patients.

Keywords: circulating cell-free DNA; esophageal squamous cell carcinoma; survival.

Figure 1

Receiver operating characteristic curve of plasma circulating cell-free DNA in 81 patients with esophageal squamous cell carcinoma and 95 normal controls. The sensitivity was 96.3% and the specificity was 94.1%; the area under the curve was 0.991 (95% confidence interval 0.982–0.999).

Figure 2

Kaplan–Meier survival curve and log-rank test of different cfDNA levels in disease-free survival (DFS) of esophageal squamous cell carcinoma (ESCC) patients. Patients with lower cfDNA levels had significantly better DFS (p = 0.013).

Figure 3

Kaplan–Meier survival curve and log-rank test of different cfDNA levels in overall survival (OS) of ESCC patients. Patients with lower cfDNA levels had better OS, but not significantly (p = 0.164).