Objective To investigate the expression and clinical significance of circular RNA(circRNA)051778 in lung adenocarcinoma-malignant pleural effusion(LA-MPE)and tuberculous pleural effusion(TPE).Methods This is a cross-sectional study.A total of 212 patients were recruited from the Jiangxi Chest Hospital between October 2018 and September 2019,and their pleural effusion samples and/or plasma samples were collected.The exosomal circRNA profile was sketched by circRNA microarray.Differentially expressed circRNAs(DECs)were verified by droplet digital PCR.In addition,a putative circRNA-miRNA-mRNA network was constructed,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were performed to predict the functions of the DECs.The diagnostic value of circRNA_051778 was evaluated by binary logistic regression and receiver operating characteristic curve.Results The expression level of circRNA_051778 in the LA-MPE samples was(3.92±0.48)copies/100 ng cDNA,while that in the TPE samples was(21.53±2.22)copies/100 ng cDNA.Compared to that in the TPE samples,circRNA_051778 was significantly downregulated in the LA-MPE samples(P＜0.001).The potential targets of circRNA_051778 were enriched in positive regulation of GTPase activity,cytoplasm,protein binding,and cancer-related pathways.The area under the curve(AUC)for the combined assessment of circRNA_051778 with liquid-based thin-layer cytology(TCT),erythrocyte sedimentation rate(ESR),and tuberculosis antibody(TBA)was 0.98(95％confidence interval:0.97-1.00),with the sensitivity being 88.0％and the specificity being 100.0％.Conclusion Exosomal circRNA_051778 is downregulated in LA-MPE.According to the findings from the GO and KEGG analyses,exosomal circRNA_051778 may play a role in cancer development and has the potential to serve as a marker for differential diagnostic of LA-MPE and TPE when it is used in combination with TCT,ESR,and TBA.