Development a glycosylated extracellular vesicle-derived miRNA Signature for early detection of esophageal squamous cell carcinoma
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 oc...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | BMC Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12916-025-03871-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832585676659359744 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Jianlin Chen |
| collection | DOAJ |
| description | 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. Graphical Abstract |
| format | Article |
| id | doaj-art-ec7d0bcbbdd04eb5900f93715e131984 |
| institution | Kabale University |
| issn | 1741-7015 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medicine |
| spelling | doaj-art-ec7d0bcbbdd04eb5900f93715e1319842025-01-26T12:37:22ZengBMCBMC Medicine1741-70152025-01-0123111510.1186/s12916-025-03871-zDevelopment a glycosylated extracellular vesicle-derived miRNA Signature for early detection of esophageal squamous cell carcinomaJianlin Chen0Yue Zheng1Zhen Wang2Qi Gao3Kun Hao4Xiongfeng Chen5Nantian Ke6Xiang Lv7Jiamiao Weng8Yuhong Zhong9Zhixin Huang10Miao Fu11Lilan Zhao12Fan Lin13Hui Mi14Haijun Tang15Chundong Yu16Yi Huang17Shengli Clinical Medical College, Fujian Medical UniversityShengli Clinical Medical College, Fujian Medical UniversityDepartment of Clinical Laboratory, Shishi HospitalResearch and development center, Beijing Youngen Technology Co. LtdResearch and development center, Beijing Hotgen Biotech Co., LtdShengli Clinical Medical College, Fujian Medical UniversityShengli Clinical Medical College, Fujian Medical UniversityShengli Clinical Medical College, Fujian Medical UniversityShengli Clinical Medical College, Fujian Medical UniversityDepartment of Clinical Laboratory, the Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Clinical Laboratory, Fujian Provincial HospitalDepartment of Clinical Laboratory, Jinhua Municipal Central HospitalShengli Clinical Medical College, Fujian Medical UniversityShengli Clinical Medical College, Fujian Medical UniversityDepartments of Clinical Laboratory, Changzhi People’s HospitalShengli Clinical Medical College, Fujian Medical UniversityShengli Clinical Medical College, Fujian Medical UniversityShengli Clinical Medical College, Fujian Medical UniversityAbstract 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 Abstracthttps://doi.org/10.1186/s12916-025-03871-zGlycosylated EVs capturemiRNALiquid biopsyEarly diagnosisEsophageal squamous cell carcinoma |
| spellingShingle | 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 Development a glycosylated extracellular vesicle-derived miRNA Signature for early detection of esophageal squamous cell carcinoma BMC Medicine Glycosylated EVs capture miRNA Liquid biopsy Early diagnosis Esophageal squamous cell carcinoma |
| title | Development a glycosylated extracellular vesicle-derived miRNA Signature for early detection of esophageal squamous cell carcinoma |
| title_full | Development a glycosylated extracellular vesicle-derived miRNA Signature for early detection of esophageal squamous cell carcinoma |
| title_fullStr | Development a glycosylated extracellular vesicle-derived miRNA Signature for early detection of esophageal squamous cell carcinoma |
| title_full_unstemmed | Development a glycosylated extracellular vesicle-derived miRNA Signature for early detection of esophageal squamous cell carcinoma |
| title_short | Development a glycosylated extracellular vesicle-derived miRNA Signature for early detection of esophageal squamous cell carcinoma |
| title_sort | development a glycosylated extracellular vesicle derived mirna signature for early detection of esophageal squamous cell carcinoma |
| topic | Glycosylated EVs capture miRNA Liquid biopsy Early diagnosis Esophageal squamous cell carcinoma |
| url | https://doi.org/10.1186/s12916-025-03871-z |
| work_keys_str_mv | AT jianlinchen developmentaglycosylatedextracellularvesiclederivedmirnasignatureforearlydetectionofesophagealsquamouscellcarcinoma AT yuezheng developmentaglycosylatedextracellularvesiclederivedmirnasignatureforearlydetectionofesophagealsquamouscellcarcinoma AT zhenwang developmentaglycosylatedextracellularvesiclederivedmirnasignatureforearlydetectionofesophagealsquamouscellcarcinoma AT qigao developmentaglycosylatedextracellularvesiclederivedmirnasignatureforearlydetectionofesophagealsquamouscellcarcinoma AT kunhao developmentaglycosylatedextracellularvesiclederivedmirnasignatureforearlydetectionofesophagealsquamouscellcarcinoma AT xiongfengchen developmentaglycosylatedextracellularvesiclederivedmirnasignatureforearlydetectionofesophagealsquamouscellcarcinoma AT nantianke developmentaglycosylatedextracellularvesiclederivedmirnasignatureforearlydetectionofesophagealsquamouscellcarcinoma AT xianglv developmentaglycosylatedextracellularvesiclederivedmirnasignatureforearlydetectionofesophagealsquamouscellcarcinoma AT jiamiaoweng developmentaglycosylatedextracellularvesiclederivedmirnasignatureforearlydetectionofesophagealsquamouscellcarcinoma AT yuhongzhong developmentaglycosylatedextracellularvesiclederivedmirnasignatureforearlydetectionofesophagealsquamouscellcarcinoma AT zhixinhuang developmentaglycosylatedextracellularvesiclederivedmirnasignatureforearlydetectionofesophagealsquamouscellcarcinoma AT miaofu developmentaglycosylatedextracellularvesiclederivedmirnasignatureforearlydetectionofesophagealsquamouscellcarcinoma AT lilanzhao developmentaglycosylatedextracellularvesiclederivedmirnasignatureforearlydetectionofesophagealsquamouscellcarcinoma AT fanlin developmentaglycosylatedextracellularvesiclederivedmirnasignatureforearlydetectionofesophagealsquamouscellcarcinoma AT huimi developmentaglycosylatedextracellularvesiclederivedmirnasignatureforearlydetectionofesophagealsquamouscellcarcinoma AT haijuntang developmentaglycosylatedextracellularvesiclederivedmirnasignatureforearlydetectionofesophagealsquamouscellcarcinoma AT chundongyu developmentaglycosylatedextracellularvesiclederivedmirnasignatureforearlydetectionofesophagealsquamouscellcarcinoma AT yihuang developmentaglycosylatedextracellularvesiclederivedmirnasignatureforearlydetectionofesophagealsquamouscellcarcinoma |