Tumor-derived Exosomes LncUEGC1 As A Circulating Biomarker For Diagnosis Of Early Gastric Cancer

Existing conventional tumor markers for non-invasive diagnosis of gastric cancer(GC)exhibit lower sensitivity and specificity when were used in the detection of early gastric cancer(EGC).Therefore,this proj ect is dedicated to screening and identifying specific exosomal 1ncRNA biomarkers for early gastric cancer,which have high sensitivity and stability for the diagnosis of EGC.In the present study,we isolated plasma exosomes from 5 healthy individuals and 10 stage I GC patients,as well as cell line culture supernatants exosomes from 4 human primary gastric epithelial cell lines(HPGECs)and 4 GC.Then,Exosomal RNA profiling was performed using RNA sequencing to screened and identify EGC-specific exosomal IncRNAs.Respectively,compared with healthy individuals and HPGECs,the expression levels of 79 and 285 exosomal RNAs were significantly up-regulated in stage I gastric cancer and gastric cancer cell lines.Through combinational analysis of the RNA sequencing results,we found two EGC-specific exosomal IncRNAs,lncUEGCl and lncUEGC2.Further real-time fluorescence quantitative PCR experiments in EGC plasma and gastric cancer cell lines(GCCs)confirmed that lncUEGC1 and lncUEGC2 were significantly up-regulated in exosomes.In addition,stability testing indicated that almost all exosomes lncUEGCl were encapsulated in the exosomes and thus protected from RNase degradation.Next,the diagnostic accuracy of the exosomal lncUEGC1 was evaluated.When lncUEGC1 distinguishes between early gastric cancer patients and healthy individuals,the AUC value is 0.8760.When lncUEGC1 differentiates patients with chronic atrophic gastritis and healthy individuals from precancerous lesions,the AUC value is 0.8406.However,the carcinoembryonic antigen has an AUC value of 0.6424 when distinguishing between early gastric cancer patients and healthy individuals.When carcinoembryonic antigen differentiates patients with chronic atrophic gastritis and healthy individuals from precancerous lesions,the AUC value is 0.6123.It can be seen that the diagnostic accuracy of IncUEGC1 is higher than carcinoembryonic antigen.The exosomal IncUEGC1 is highly sensitive,stable and non-invasive to the diagnosis of early gastric cancer.Therefore,it is expected to develop biomarkers for the diagnosis of early gastric cancer.