Diagnostic and prognostic value of plasma cell-free DNA combined with VEGF-C in laryngeal squamous cell carcinoma

Background: Circulating cell-free DNA (cfDNA) and vascular endothelial growth factor-C (VEGF-C) can be utilized to detect cancer and predict its prognosis. However, their potential application in laryngeal squamous cell carcinoma (LSCC) is unclear.Purpose: This study aimed to identify the diagnostic and prognostic value of cfDNA and VEGF-C in LSCC patients.Methods: The plasma cfDNA of 148 LSCC patients and 43 non-tumor patients were isolated. Quantitative real-time PCR (qRT-PCR) was performed to assess long and short DNA fragments in plasma by amplifying the ALU repeats. ALU-qPCR results (ALU247/ALU115) were used to calculate cfDNA integrity index. Vascular endothelial growth factor-C (VEGF-C) level was detected by ELISA assay. Correlation between cfDNA and clinical features was analyzed. For detecting the sensitivity and specificity of cfDNA and VEGF-C alone or in combination for diagnosing LSCC, receiver operator characteristic (ROC) was established. For evaluating the overall survival (OS) of LSCC, Kaplan-Meier curves were established. Results: LSCC patients had significantly higher levels of plasma cfDNA (ALU115, ALU247, and cfDNA integrity index) and VEGF-C than those without cancer (p < 0.05), showing area under the curve (AUC) values of 0.79, 0.74, 0.62 and 0.80, when cutoff value was correspondingly defined at 2.14 ng/mL, 1.39 ng/mL, 0.73 and 412.90 pg/mL, respectively. The AUC for distinguishing LSCC patients from non-tumor patients by plasma cfDNA combined with VEGF-C was 0.89 (95% CI: 0.83-0.94). A significant correlation was found between plasma cfDNA levels and Ki-67, tumor size, pT stage, and smoking history (p < 0.05). Based on survival analysis, low VEGF-C concentration groups had longer OS than those with high VEGF-C concentration (p = 0.02).Conclusion: Indicators such as plasma cfDNA and VEGF-C may be used to diagnose and monitor LSCC for its noninvasiveness and rapid accessibility.