Diagnostic value of protein markers in plasma exosomes of lung squamous cell carcinoma

Objective To investigate the tumor-associated protein molecules carried by plasma exosomes of patients with lung squamous cell carcinoma before treatment and analyze their value as clinical markers. Methods Exosomes from 2 patients with lung squamous cell carcinoma before treatment and 2 healthy controls were collected by ultracentrifugation. Proteomics was applied to analyze the protein expression profiles of exosomes. Candidate molecules were verified in another 30 exosomes samples from lung squamous cell carcinoma and healthy controls using enzyme-linked immunosorbent assay (ELISA). Results Electron microscopy and particle-counting assay showed that high-quality exosomes were collected. The number of exosomes distributed from 45 to 135 nm in 2 cases of lung cancer patients were 7.89×1011/ml and 9.71×1011/ml, respectively, significantly higher than 2.76×1011/ml and 1.41×1011/ml in healthy controls. Proteomic analysis showed that proteins of exosomes in lung squamous cell carcinoma patients were very different from those of healthy controls, and some proteins are related to important functions in tumor progression. 14-3-3ζ from exosomes was selected and further verified as a marker, and the area under the receiver operating characteristic curve (ROC) was 0.68. The sensitivity and specificity of 14-3-3 ζ from exosomes were 60.0% and 80.0%, respectively, suggested that it could be used as a diagnostic marker for lung squamous cell carcinoma. Conclusion The exosome counts in plasma and the protein molecules from exosomes, such as 14-3-3ζ, are closely related to the tumorigenesis, which can be used to assist clinical diagnosis of lung squamous cell carcinoma patients. Key words: Lung neoplasms, squamous cell carcinoma; Exosomes; 14-3-3ζ; Proteomics; Diagnosis