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<p>Esophageal squamous cell carcinoma (ESCC) remains a major contributor to cancer-related mortality, with molecular residual disease (MRD) detection posing a significant challenge in post-surgical management. This study aimed to evaluate the effectiveness of circulating tumor DNA (ctDNA) in detecting MRD in patients with resectable ESCC undergoing radical surgery. A total of 62 primary tumor tissues, 108 preoperative, and 125 postoperative plasma samples were collected from 125 such ESCC patients who underwent radical surgery, and subjected to sequencing. Next-Generation Sequencing and ultra-high sensitivity Automated Triple Groom Sequencing panels were used to sequence genomic DNA from tumor tissues and ctDNA from plasma, respectively. ctDNA positive mutations included tumor-informed mutations and tumor-naïve mutations. Key findings revealed a high concordance rate of mutation detection between primary tumor tissue and preoperative plasma samples (91.11%, <i>p</i> = 0.62). Critically<b>,</b> the recurrence rate was higher in postoperative ctDNA-positive ESCCs than that in negative ones (66.67% (40/60) vs. 21.54% (14/65), <i>p</i> &lt; 0.001). And postoperative ctDNA-positivity was associated with poorer disease-free survival (DFS) (hazard ratio (HR): 4.58, 95% CI: 2.65–7.92, <i>p</i> &lt; 0.001) and overall survival (OS) (HR: 5.39, 95% CI: 2.96–9.80, <i>p</i> &lt; 0.001). Similar prognostic patterns were observed in patients with preoperative ctDNA-positivity (<i>p</i> = 0.014; <i>p</i> = 0.016; <i>p</i> = 0.071) and ctDNA-nonclearance (<i>p</i> &lt; 0.001; <i>p</i> &lt; 0.001; <i>p</i> &lt; 0.001). Furthermore, in combination with postoperative ctDNA status, the Tumor-Node-Metastasis-Blood (TNMB) staging system was able to better distinguish patients with different prognoses compared with traditional TNM (<i>p</i> &lt; 0.001). In conclusion, postoperative ctDNA-positivity emerges as a promising biomarker for detecting MRD in ESCC patients following surgical resection.</p>

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Circulating tumor DNA as a marker of molecular residual disease in resected esophageal squamous cell carcinoma

  • 期刊论文

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  • 发表日期：

    2025年9月18日

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  • Cai-Yan Fang,
  • Jing Wen,
  • Jia-Di Wu,
  • Zhi-Chao Li,
  • Sheng Huang,
  • Yan Huang,
  • Ji-Yang Chen,
  • Hui-Lin Su,
  • Xiu-Ying Xie,
  • Kong-Jia Luo,
  • Jian-Hua Fu,
  • Hong Yang

摘要

Esophageal squamous cell carcinoma (ESCC) remains a major contributor to cancer-related mortality, with molecular residual disease (MRD) detection posing a significant challenge in post-surgical management. This study aimed to evaluate the effectiveness of circulating tumor DNA (ctDNA) in detecting MRD in patients with resectable ESCC undergoing radical surgery. A total of 62 primary tumor tissues, 108 preoperative, and 125 postoperative plasma samples were collected from 125 such ESCC patients who underwent radical surgery, and subjected to sequencing. Next-Generation Sequencing and ultra-high sensitivity Automated Triple Groom Sequencing panels were used to sequence genomic DNA from tumor tissues and ctDNA from plasma, respectively. ctDNA positive mutations included tumor-informed mutations and tumor-naïve mutations. Key findings revealed a high concordance rate of mutation detection between primary tumor tissue and preoperative plasma samples (91.11%, p = 0.62). Critically, the recurrence rate was higher in postoperative ctDNA-positive ESCCs than that in negative ones (66.67% (40/60) vs. 21.54% (14/65), p < 0.001). And postoperative ctDNA-positivity was associated with poorer disease-free survival (DFS) (hazard ratio (HR): 4.58, 95% CI: 2.65–7.92, p < 0.001) and overall survival (OS) (HR: 5.39, 95% CI: 2.96–9.80, p < 0.001). Similar prognostic patterns were observed in patients with preoperative ctDNA-positivity (p = 0.014; p = 0.016; p = 0.071) and ctDNA-nonclearance (p < 0.001; p < 0.001; p < 0.001). Furthermore, in combination with postoperative ctDNA status, the Tumor-Node-Metastasis-Blood (TNMB) staging system was able to better distinguish patients with different prognoses compared with traditional TNM (p < 0.001). In conclusion, postoperative ctDNA-positivity emerges as a promising biomarker for detecting MRD in ESCC patients following surgical resection.