AUTHOR=Liu Tao , Yao Qianqian , Jin Hai TITLE=Plasma Circulating Tumor DNA Sequencing Predicts Minimal Residual Disease in Resectable Esophageal Squamous Cell Carcinoma JOURNAL=Frontiers in Oncology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.616209 DOI=10.3389/fonc.2021.616209 ISSN=2234-943X ABSTRACT=

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.