Increased serum cell-free DNA levels in relation to inflammation are predictive of distant metastasis of esophageal squamous cell carcinoma

Abstract

Distant metastasis hinders a favorable outcome for patients with esophageal squamous cell carcinoma (ESCC) by limiting the surgical cure. The levels of cell-free DNA (cfDNA) in the blood have served as a predictor for metastasis and recurrence in distant organs in liver cancer. Thus, this study tested the clinical efficacy of serum cfDNA levels as a predictive marker for distant metastasis of ESCC. We investigated cfDNA levels in a cohort of 101 ESCC patients and 46 age- and gender-matched control patients with benign disease. We found that serum cfDNA levels were significantly higher in the ESCC patients than in the control patients (P=0.034). In the ESCC patients, serum cfDNA levels were positively associated with tumor size and cytokeratin 19 fragment (CYFRA 21-1) expression (r=0.416 and r=0.573, respectively). An increase in cfDNA levels was also associated with host inflammation status including C-reactive protein levels and neutrophil and monocyte numbers in the peripheral blood. Serum cfDNA levels tended to be higher in advanced tumors when compared to early stage tumors. We found that serum cfDNA levels were significantly higher in ESCC patients with distant metastasis than in those without (P=0.011). Logistic regression analysis showed that serum cfDNA levels represented only one independent risk factor for distant metastasis among the five factors tested including gender, age, cfDNA levels, CYFRA 21-1 and squamous cell carcinoma antigen levels (P=0.0414). These results suggest that increased serum cfDNA levels may serve as a useful predictor for distant metastasis of ESCC.