Proteomic analysis of small extracellular vesicles unique to cervical cancer.

Abstract

Cervical cancer (CC) is the fourth most common cancer in females worldwide. Existing biomarkers for CC, such as squamous cell carcinoma antigens, show low specificity. Hence, a novel biomarker for the diagnosis of CC is required. Through proteomic analysis, this study aimed to distinguish between the small extracellular vesicle (sEV) protein profiles of healthy controls (HC) and CC sera and to identify potential sEV proteins that can serve as biomarkers for CC diagnosis. The number and size distribution of sEVs in HC and CC sera were measured using nanoparticle tracking analysis. Differential ultracentrifugation combined with size-exclusion chromatography was used to isolate and purify sEVs. Liquid chromatography-tandem mass spectrometry was used to identify and compare the protein profiles between patients with CC and HC. Differentially expressed extracellular vesicle (EV) proteins were validated using The Cancer Genome Atlas database. The EV particle concentration in patients with CC was marginally higher than that in HC. Proteomic and functional protein analyses revealed a difference in the EV protein profiles between HC and CC and identified proteins that can serve as biomarkers for CC. This study provides insights into the potential of sEVs as less invasive biomarkers for CC diagnosis. Validation with a well-designed cohort should be performed to determine the clinical diagnostic value of specific protein markers for CC.