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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.
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Objective To study the differential diagnostic efficacy of α-enolase ( ENO1 ) autoantibodies in lung adenocarcinoma , benign pulmonary disease , and normal individuals , and to evaluate the improvement of the diagnostic efficiency of existing markers by establishing a binary logistic regression model.Methods This was a case-control study.Participants were from the public health welfare program led by the National Cancer Center/Chinese Academy of Medical Sciences Peking Union Medical College Cancer Hospital.Serum samples were collected June 2014 to June 2017 including 60 patients with lung adenocarcinoma , 50 patients with benign lung diseases , and 90 healthy controls.Luminex MAGPIX platform was applied to detect serum ENO1 autoantibodies, CEA and Cyfra21-1 proteins.The receiver operating characteristic curve (ROC)analysis and binary logistic regression were used to evaluate the performance and build diagnostic model.Results The median level of serum ENO1 autoantibody in patients with lung adenocarcinoma was 918.5 ( 665.5-2 043.3 ), which was significantly higher than that in the normal individuals (722.5, 585.5-921.8, Z＝-3.113, P＝0.002) and benign lung disease patients (693.0, 501.4-973.3, Z＝-3.395, P＝0.001).And no significant differences between benign disease groups and normal individuals (Z＝-1.155, P＝0.248).ROC was plotted, and the area under the curve (AUC) of ENO1 autoantibodies was 0.664 (95% confidence interval : 0.576-0.752), while the AUCs of existing diagnostic marker CEA and Cyfra21-1 were 0.680 (95% confidence interval : 0.594-0.767) and 0.617 (95% confidence interval: 0.532-0.703).A joint diagnostic model including ENO1 and CEA was built with an AUC of 0.757 (95%confidence interval : 0.675-0.838).The diagnostic efficacy of the model was significantly different from ENO1 autoantibodies (Z＝2.648, P＝0.008).When the specificity was 90%, the sensitivity of ENO1 autoantibodies was 38.3%, while the sensitivity of the combination with CEA was raised to 50%.Conclusion ENO1 autoantibodies could be a marker for the auxiliary diagnosis of lung adenocarcinoma, and can improve the efficacy of the existing diagnostic markers such as CEA .ENO1 has the potential use for the diagnosis and screening.