Glypican-1 in Serum-Derived Exosomes As a Potential Biomarker in Liquid Biopsy of Non-Small Cell Lung Cancer

BACKGROUND: Glypican-1 (GPC1) identifies cancer exosomes and detects early pancreatic cancer. This study was to investigate the level of glypican-1 in serum-derived exosomes from non-small-cell lung cancer (NSCLC) patients and its potential value in clinical application. METHODS: Exosomes were isolated from serum by ultracentrifugation and identified. Levels of GPC1 in the exosomes were quantified by Western blotting, while GCP1 expression that in tumor tissue was quantified by immunohistochemistry. The Kaplan Meier plotter was used to determine the relationship between levels of GCP1 and overall survival. Data were compared among groups by one-way analysis of variance with least significant difference post-test for further pair-wise comparisons. RESULTS: Levels of GPC1 in serum-derived exosomes were significantly higher in the preoperative untreated NSCLC group than in the post-surgery, benign pulmonary nodule and healthy control groups. Levels of GPC1 in the exosomes were also significantly higher in late-stage disease (stages III/IV) than in early-stage disease (stages I/II). Adenocarcinoma and the presence of vascular carcinoma embolus were both associated with higher levels of GPC1 in the exosomes. Levels of GPC1 in serum-derived exosomes correlated well with that in the tumor tissue. NSCLC patients with high expression of GPC1 had a significantly lower 250-month survival rate than those with low levels of GPC1. CONCLUSIONS: Levels of GPC1 in serum-derived exosomes can distinguish NSCLC patients from healthy subjects and even patients with a benign lung disease, correlate with tumor burden and stage, and can separate patients with early stage NSCLC from late, and affect the prognosis and survival of NSCLC patients.