Analysis Of LncRNA Expression Profile Of Plasma Exosomes On Patients Esophageal Carcinoma With The Review Of The Literature

BackgroundsChina is a country with the biggest number of esophageal cancer cases in the world,where more than 200,000 patients died of esophageal squamous cell carcinoma(ESCC)each year.However,the majority of patients with early-stage ESCC have no obvious symptoms and most ESCC patients are usually diagnosed at advanced stage.Since the prognosis of early-stage ESCC is much better than that of advanced-stage,diagnosis of ESCC at early stage is very important for the improvement of prognosis.Liquid biopsy is emerging as a promising diagnostic approach that focuses on detection of the bioactive substances in blood or other body fluids.Long non-coding RNAs(LncRNAs)are involved in a variety of cellular activities including the tumorgenesis and progression of tumors.Exosomes are bilayered micro vesicles existing in blood or other kinds of body fluids,secreted by most kinds of cells including tumor cells.LncRNAs of tumor cells can be selectively enriched and maintain great completeness in exosomes.We hypothesize that detection of exosomal lncRNAs may help to improve diagnosis of early-stage ESCC.Methods1.Plasma samples were obtained from 6 patients with ESCC,6 cases of esophagitis and 6 subjects of age/gender-matched healthy individuals,respectively.2.Exosomes were isolated from plasma by Ribo Exosomes Isolation Reagent Kit.Characterization of the isolated exosomes was determined by ZETASIZER Nano series-Nano-ZS instrument.The exosomal surface markers,CD81 and CD63,were detected using the anti-CD63 and anti-CD81 by Accuri C6 Flow Cytometer.3.RNA-sequencing was used to profile exosomal lncRNAs and mRNAs.4.We analyze the exosomal sequencing data with multiple softwares,and align the clean reads to the human reference genome assembly(GRCh38)to define mRNA and ncRNA profiles.5.q RT-PCR was applied to verify the expression levels of lncRNAs and mRNAs.Results1.The landscape of exosomal lncRNAs from early-stage ESCC,esophagitis and subjects with normal esophagus can be depicted.2.We showed that over 80% of exosomal lncRNAs are intergenic subclass.2.We found that lncRNAs exhibit tighter tissue-specificity,higher expression levels,and lower splicing efficiency than that of mRNAs in exosomes.3.We identified that 124 dysregulated exosomal lncRNAs that distinguish early-stage ESCC from esophagitis,reflecting different underlying regulatory mechanisms.Among them,exosomal lncRNAs(FAM138D,AL589739.1,AC008105.2,PTOV1-AS2,AC068134.2,WI2-85898F10.1)are promising to serve as lncRNA signature for ESCC.Conclusion1.We get the exosomal lncRNAs and mRNA genome landscape of ESCC patients.2.Exosomal lncRNAs have greater potential than exosomal mRNAs to serve as disease biomarkers.3.Specific exosomal lncRNAs profile can be a promising diagnosis tool for early-stage of early-stage.