Journal
FRONTIERS IN ONCOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.616209
Keywords
esophageal squamous cell carcinoma; circulating tumor DNA; next-generation sequencing; minimal residual disease; prognostic marker
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Funding
- Shanghai Science and Technology Committee [15411951700]
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Esophageal squamous cell carcinoma (ESCC) is a lethal cancer with high recurrence rates and early detection challenges. Circulating tumor DNA (ctDNA) is emerging as a useful biomarker for non-invasive diagnosis and monitoring tumor prognosis. Analysis of plasma cell-free DNA (cfDNA) variations in ESCC patients revealed correlation between postoperative cfDNA detection and shorter overall survival as well as higher relapse rates.
Esophageal squamous cell carcinoma (ESCC) is lethal as tumors are rarely detected at an early stage and have a high recurrence rate. There are no particularly useful biomarkers for the prognostic prediction of ESCC. Circulating tumor DNA (ctDNA) is becoming an important biomarker for non-invasive diagnosis and monitoring tumor prognosis. Here, we aimed to analyze variations in plasma cell-free DNA (cfDNA) amount to search for minimal residual disease (MRD). Plasma and white blood cells (WBCs) of 60 patients were collected before tumor resection and a week after surgery. Tumor specimens were also collected as formalin-fixed paraffin-embedded (FFPE) samples. All samples were extracted to analyze the genetic alterations of 61 genes using capture-based next-generation sequencing (NGS). Tumor variants were detected in 38 patients with ESCC, and the two driver genes with the highest mutation frequency were TP53 and PIK3CA. Of the pre-surgical plasma cfDNA samples, 73.7% of identified variants matched the tissue. In patients who did not receive adjuvant therapy after surgery, postoperative cfDNA-positive patients had shorter overall survival (hazard ratios (HR), 25.8; 95% CI, 2.7-242.6; P = 0.004) and were more likely to relapse than postoperative cfDNA-negative patients (HR, 184.6; 95% CI, 3.6-9576.9; P = 0.01). Detection of ctDNA after surgical tumor excision is associated with tumor relapse and disease-specific survival, and can be used as a prognostic biomarker for MRD detection in ESCC.
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