Biomarker research · 2025
Development and validation of predictive models combining cell-Free DNA motifs and protein biomarkers for early detection of esophageal squamous cell carcinoma and precancerous lesion.
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Ma Liu, Dou Lizhou, Liu Yong, Zhang Yueming, Liu Xudong, Ng Hoi-Loi, Chu Jiangtao, Liu Yumeng, Li Zhengqi, Ke Yan, Liu Siyao, He Shun, Wang Guiqi
Аннотация
BACKGROUND: Detecting and treating precancerous lesions can lower the incidence of esophageal squamous cell carcinoma (ESCC), making it a key preventive strategy. Although endoscopic screening and intervention can significantly reduce mortality associated with ESCC, they have certain shortcomings. We aimed to develop three predictive models: the motif, eight-protein, and combined motif-protein models to identify ESCC and its precancerous lesions.
METHODS: Plasma samples were collected for cfDNA sequencing, and nine commonly used clinical protein biomarkers related to the digestive system were measured. Using a total cohort of 199 patients with ESCC, 91 patients with esophageal squamous precancerous lesions (ESPL), and 201 controls, we developed an integrative model based on selected multi-omics biomarkers.
RESULTS: The motif-protein model, integrating 20 principal components of cfDNA terminal motifs with six protein features, outperformed both the motif model and the eight-protein model in distinguishing patients with ESCC and ESPL (area under the curve = 0·90). It achieved an overall sensitivity of 88·5% and a specificity of 75·4%. Notably, it successfully identified 90·9% of high-grade intraepithelial neoplasia cases, 86·8% of stage I ESCC cases, and 87·8% of HGIN or T1aN0 stage ESCC (subset of Stage I) cases who were eligible for endoscopic treatment, highlighting its potential as an effective tool for early diagnosis.
CONCLUSIONS: The motif-protein model may serve as an effective tool for the early diagnosis of esophageal lesions. Our findings underscore the clinical potential of the multi-omics liquid biopsy test as a non-invasive method for detecting early esophageal lesions.
METHODS: Plasma samples were collected for cfDNA sequencing, and nine commonly used clinical protein biomarkers related to the digestive system were measured. Using a total cohort of 199 patients with ESCC, 91 patients with esophageal squamous precancerous lesions (ESPL), and 201 controls, we developed an integrative model based on selected multi-omics biomarkers.
RESULTS: The motif-protein model, integrating 20 principal components of cfDNA terminal motifs with six protein features, outperformed both the motif model and the eight-protein model in distinguishing patients with ESCC and ESPL (area under the curve = 0·90). It achieved an overall sensitivity of 88·5% and a specificity of 75·4%. Notably, it successfully identified 90·9% of high-grade intraepithelial neoplasia cases, 86·8% of stage I ESCC cases, and 87·8% of HGIN or T1aN0 stage ESCC (subset of Stage I) cases who were eligible for endoscopic treatment, highlighting its potential as an effective tool for early diagnosis.
CONCLUSIONS: The motif-protein model may serve as an effective tool for the early diagnosis of esophageal lesions. Our findings underscore the clinical potential of the multi-omics liquid biopsy test as a non-invasive method for detecting early esophageal lesions.