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Proteomic Analysis of Extracellular Vesicles Reveals Vitronectin and Laminin Subunit Alpha-3 as Candidate Biomarkers for Gastric Cancer

Year: 2026

Type: article

Abstract: Background/Aims: Clinically useful noninvasive biomarkers for gastric cancer remain limited. Extracellular vesicles (EVs) carry a molecular cargo reflective of their cells of origin and have emerged as promising candidates for blood-based cancer biomarkers. We aimed to identify EV-associated protein biomarkers for gastric cancer via a proteomic approach. Methods: Proteomic profiling of EVs was performed using one normal gastric cell line (Hs738st/int) and two gastric cancer cell lines (AGS and NCI-N87). Selected proteins were validated in blood-derived EVs isolated from plasma samples of 10 healthy controls and 36 patients with gastric cancer. Results: Proteomic analysis identified 224 differentially expressed proteins whose expression was consistently altered in gastric cancer cell line-derived EVs. Among these, vitronectin (VTN) and laminin subunit alpha-3 (LAMA3) were selected based on their consistent upregulation. EV-associated LAMA3 levels were significantly higher in patients with gastric cancer than in healthy controls (p=0.003), with significant elevations observed from stage II onward (p=0.041, p=0.017, and p=0.004 for stages II, III, and IV, respectively). EV-associated VTN levels were not significantly different overall (p=0.089); however, stage-specific analysis demonstrated significant increases in VTN levels in patients with stage III (p=0.036) and stage IV (p=0.005) gastric cancer. Both EV-associated VTN and LAMA3 levels showed significant positive correlations with the cancer stage (ρ=0.564 and ρ=0.611, respectively; both p<0.001). Conclusions: The levels of EV-associated VTN and LAMA3 appear to be more closely associated with disease progression than with early-stage detection of gastric cancer. These findings suggest that EV-based proteomic biomarkers may have clinical utility for monitoring tumor progression in patients with clinically advanced gastric cancer.

Source: Gut and Liver

DOI: 10.5009/gnl250470

Authors: Dong Chan Joo, Su Jin Park, Gwang Ha Kim, Moon Won Lee, Bong Eun Lee

Institutions: Pusan National University Hospital, Pusan National University

Language: English

Topic: Extracellular vesicles in disease

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond

Funders: Pusan National University, Pusan National University Hospital, Korean College of Helicobacter and Upper Gastrointestinal Research