Integrative analysis of saliva-derived exosomal proteome and lipidome for the diagnosis of esophageal squamous cell carcinoma

Wei Zhong ¹, Jian Liu ¹, Junhua Xie ²

⁰Department of Thoracic Surgery and Lung Transplantation, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, China.

Bmc Cancer +

|

August 2, 2025

View abstract on PubMed

Summary

Early diagnosis of esophageal squamous cell carcinoma (ESCC) is vital. Salivary exosome proteomic and lipidomic analysis revealed significant differences, with lipid features showing high potential for non-invasive ESCC diagnosis.

Area Of Science

Biochemistry
Oncology
Proteomics
Lipidomics

Background

Early diagnosis of esophageal squamous cell carcinoma (ESCC) is critical for patient outcomes.
Current ESCC diagnosis relies on invasive endoscopic biopsies.
Salivary exosomes offer potential for non-invasive screening, but their molecular profiles are largely uncharacterized.

Purpose Of The Study

To investigate the proteomic and lipidomic characteristics of salivary exosomes in ESCC patients.
To identify potential biomarkers for non-invasive ESCC diagnosis.
To explore the role of salivary exosome alterations in ESCC development and progression.

Main Methods

Salivary exosomes were isolated from ESCC patients and healthy controls via ultracentrifugation.
Non-targeted proteomic and lipidomic analyses were performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Differential expression analysis and multi-omics correlation analysis were employed to identify significant molecular changes.

Main Results

Significant proteomic and lipidomic differences were identified between ESCC patients and controls.
ESCC proteomic profiles indicated alterations in immune responses and tissue homeostasis.
Multi-omics analysis suggested ESCC influences fatty acid metabolism and the oral immune microenvironment.
A diagnostic model using 28 lipid features achieved perfect diagnostic performance (AUC=1.000).

Conclusions

Salivary exosomes exhibit distinct proteomic and lipidomic alterations in ESCC patients.
These molecular changes offer novel insights into ESCC pathogenesis.
Lipid features in salivary exosomes demonstrate high potential for accurate and non-invasive ESCC diagnosis, warranting further validation.

Keywords:

Diagnosis Esophageal squamous cell carcinoma Exosomes Lipidomics Proteomics

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