Scholarlink

Background <p>Esophageal squamous cell carcinoma (ESCC) is often diagnosed at an advanced stage due to the lack of non-invasive early detection tools, which significantly impacts patient prognosis. Given that glycosylation alterations especially high sialylation and fucosylation, frequently occur during cellular malignant transformation, but their roles are not elucidated. We examined alterations in disease-specific glycosylated extracellular vesicles (EVs)-derived miRNAs in the serum of ESCC patients, evaluating their utility as diagnostic biomarkers.</p> Methods <p>A total of 371 ESCC and 303 healthy controls (HCs) were recruited in this multi-stage, multicentre case-control study. Fucosylated (Fuc-) and sialylated (Sia-) EVs were isolated utilizing Lentil lectin (LCA) and wheat germ lectin (WGA)-coated magnetic beads, respectively. The glycosylated EVs-derived miRNAs-based signature (Riskscore<sup>Fuc−&amp;Sia−</sup>) was established through logistic regression in a training cohort and subsequently validated in an internal and an external multicentre cohort.</p> Results <p>The Riskscore<sup>Fuc−&amp;Sia−</sup> effectively identified ESCC across all stages, demonstrating high AUC values in training (0.980), internal validation (0.957), and external multicentre validation (0.973) cohorts, markedly higher than carcinoembryonic antigen (CEA) (AUC = 0.769, training cohort; AUC = 0.749, internal validation cohort; AUC = 0.765, external validation cohort). Notably, this score exhibited robust accuracy in detecting CEA (-) ESCC cases (CEA &lt; 5&#xa0;ng/ml) (AUC = 0.974, training &amp; internal cohort; AUC = 0.973, external multicentre validation cohort). Additionally, it displayed strong efficacy in differentiating early-stage ESCC patients (AUC = 0.982, training cohort; AUC = 0.977, external multicentre validation cohort).</p> Conclusions <p>Our study illustrates the effectiveness of glycosylated EVs capture strategy for isolating tumour-specific EVs. The unique glycosylated EVs-derived miRNAs-based signature shows the optimal potential as a biomarker for early detection of ESCC.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Development a glycosylated extracellular vesicle-derived miRNA Signature for early detection of esophageal squamous cell carcinoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年1月23日

查看全文
  • Jianlin Chen,
  • Yue Zheng,
  • Zhen Wang,
  • Qi Gao,
  • Kun Hao,
  • Xiongfeng Chen,
  • Nantian Ke,
  • Xiang Lv,
  • Jiamiao Weng,
  • Yuhong Zhong,
  • Zhixin Huang,
  • Miao Fu,
  • Lilan Zhao,
  • Fan Lin,
  • Hui Mi,
  • Haijun Tang,
  • Chundong Yu,
  • Yi Huang

摘要

Background

Esophageal squamous cell carcinoma (ESCC) is often diagnosed at an advanced stage due to the lack of non-invasive early detection tools, which significantly impacts patient prognosis. Given that glycosylation alterations especially high sialylation and fucosylation, frequently occur during cellular malignant transformation, but their roles are not elucidated. We examined alterations in disease-specific glycosylated extracellular vesicles (EVs)-derived miRNAs in the serum of ESCC patients, evaluating their utility as diagnostic biomarkers.

Methods

A total of 371 ESCC and 303 healthy controls (HCs) were recruited in this multi-stage, multicentre case-control study. Fucosylated (Fuc-) and sialylated (Sia-) EVs were isolated utilizing Lentil lectin (LCA) and wheat germ lectin (WGA)-coated magnetic beads, respectively. The glycosylated EVs-derived miRNAs-based signature (RiskscoreFuc−&Sia−) was established through logistic regression in a training cohort and subsequently validated in an internal and an external multicentre cohort.

Results

The RiskscoreFuc−&Sia− effectively identified ESCC across all stages, demonstrating high AUC values in training (0.980), internal validation (0.957), and external multicentre validation (0.973) cohorts, markedly higher than carcinoembryonic antigen (CEA) (AUC = 0.769, training cohort; AUC = 0.749, internal validation cohort; AUC = 0.765, external validation cohort). Notably, this score exhibited robust accuracy in detecting CEA (-) ESCC cases (CEA < 5 ng/ml) (AUC = 0.974, training & internal cohort; AUC = 0.973, external multicentre validation cohort). Additionally, it displayed strong efficacy in differentiating early-stage ESCC patients (AUC = 0.982, training cohort; AUC = 0.977, external multicentre validation cohort).

Conclusions

Our study illustrates the effectiveness of glycosylated EVs capture strategy for isolating tumour-specific EVs. The unique glycosylated EVs-derived miRNAs-based signature shows the optimal potential as a biomarker for early detection of ESCC.

Graphical Abstract