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

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Title: Development a glycosylated extracellular vesicle-derived miRNA Signature for early detection of esophageal squamous cell carcinoma.
Authors: Chen, Jianlin1,2 (AUTHOR), Zheng, Yue1,2 (AUTHOR), Wang, Zhen3 (AUTHOR), Gao, Qi4 (AUTHOR), Hao, Kun5 (AUTHOR), Chen, Xiongfeng1,6 (AUTHOR), Ke, Nantian1,2 (AUTHOR), Lv, Xiang1,2 (AUTHOR), Weng, Jiamiao1,2 (AUTHOR), Zhong, Yuhong7 (AUTHOR), Huang, Zhixin2,8 (AUTHOR), Fu, Miao9 (AUTHOR), Zhao, Lilan1,10 (AUTHOR), Lin, Fan1,11,12 (AUTHOR), Mi, Hui13 (AUTHOR), Tang, Haijun1,14 (AUTHOR) tanghaijun16@163.com, Yu, Chundong1,14,15 (AUTHOR) cdyu@xmu.edu.cn, Huang, Yi1,2,14,16,17 (AUTHOR) hyi8070@126.com
Source: BMC Medicine. 1/23/2025, Vol. 23 Issue 1, p1-15. 15p.
Subject Terms: *SQUAMOUS cell carcinoma, *CELL transformation, *WHEAT germ, *CARCINOEMBRYONIC antigen, *EXTRACELLULAR vesicles
Abstract: 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. [ABSTRACT FROM AUTHOR]
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  Data: Development a glycosylated extracellular vesicle-derived miRNA Signature for early detection of esophageal squamous cell carcinoma.
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  Data: &lt;searchLink fieldCode=&quot;JN&quot; term=&quot;%22BMC+Medicine%22&quot;&gt;BMC Medicine&lt;/searchLink&gt;. 1/23/2025, Vol. 23 Issue 1, p1-15. 15p.
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  Data: *&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22SQUAMOUS+cell+carcinoma%22&quot;&gt;SQUAMOUS cell carcinoma&lt;/searchLink&gt;&lt;br /&gt;*&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22CELL+transformation%22&quot;&gt;CELL transformation&lt;/searchLink&gt;&lt;br /&gt;*&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22WHEAT+germ%22&quot;&gt;WHEAT germ&lt;/searchLink&gt;&lt;br /&gt;*&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22CARCINOEMBRYONIC+antigen%22&quot;&gt;CARCINOEMBRYONIC antigen&lt;/searchLink&gt;&lt;br /&gt;*&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22EXTRACELLULAR+vesicles%22&quot;&gt;EXTRACELLULAR vesicles&lt;/searchLink&gt;
– Name: Abstract
  Label: Abstract
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  Data: 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−&amp;Sia−) was established through logistic regression in a training cohort and subsequently validated in an internal and an external multicentre cohort. Results: The RiskscoreFuc−&amp;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 &lt; 5 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). 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. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
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  Data: &lt;i&gt;Copyright of BMC Medicine is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder&#39;s express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.&lt;/i&gt; (Copyright applies to all Abstracts.)
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