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Predictive value of plasma exosomal deleted in lymphocytic leukemia 1 level in immunotherapy response of epidermal growth factor receptor/anaplastic lymphoma kinase wild type advanced non-small cell lung cancer patients |
LIU Qiuxia JI Longfei HU Yanqin PAN Nannan QIANG Xinhua LI Yong |
Department of Laboratory, the First People’s Hospital of Huzhou, Zhejiang Province, Huzhou 313000, China |
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Abstract Objective To investigate the clinical significance of plasma exosomal deleted in lymphocytic leukemia 1 (exo- DLEU1) in predicting immunotherapy response of epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) wild type advanced non-small cell lung cancer (NSCLC) patients. Methods The blood samples of 91 patients with EGFR/ALK wild type advanced NSCLC who received immunotherapy in the First People’s Hospital of Huzhou, Zhejiang Province from June 2017 to February 2019 were collected and divided into response group (53 cases) and non-response group (38 cases) according to the response after immunotherapy. Plasma exosomes were extracted from the two groups before treatment, and exoDLEU1 expression was detected by real-time fluorescent quantitative PCR. The influencing factors of immunotherapy response in EGFR/ALK wild type advanced NSCLC patients were analyzed by logistic regression. Receiver operator characteristic (ROC) curve was plotted to evaluate the predictive value of plasma exoDLEU1 level in immunotherapy response. Results Under transmission electron microscopy, the vesicles had circular or elliptical membranes with diameters ranging from 30 to 150 nm, and the original concentration was 6.6×1010 particles /ml. Flow cytometry and Western blot showed that the extracts contained exosome markers CD63, CD9, CD81, and heat shock protein 70. Real-time fluorescence quantitative PCR results showed that the plasma exoDLEU1 level in the response group before treatment was lower than that in the non-response group, and the difference was statistically significant (P<0.05). Analysis of influencing factors showed that plasma exoDLEU1 expression level was an independent influencing factor for immunotherapy non-response in EGFR/ALK wild type advanced NSCLC patients (OR=6.119, 95%CI: 2.768-13.526, P<0.05). ROC curve analysis showed that plasma exoDLEU1 expression level predicted immunotherapy response of EGFR/ALK wild type advanced NSCLC patients with an area under the curve of 0.900 (P<0.05). Conclusion The plasma exoDLEU1 level of EGFR/ALK wild type advanced NSCLC patients before immunotherapy can be used as an indicator to predict their treatment response, and help to screen out patients who are more likely to benefit from immunotherapy in the clinic.
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