Evaluation Of Pleural Fluid MiR-21,miR-29c And MiR-182 In Diagnosing Malignant Pleural Effusion

Background and objective:The differential diagnosis between benign and malignant pleural effusions is a common clinical problem.Disease of malignant pleural effusion progresses rapidly,and the median survival time is poor.Early diagnosis and timely treatment can improve the prognosis of the patients.At present,diagnosing methods for malignant pleural effusion include the detection of biomarkers such as carcino embryonic antigen?CEA?,neuron-specific enolase?NSE?and squamous cell carcinoma antigen?SCC?etc,and analysis of exfoliative cytopathology in pleural fluids,as well as histopathological examination by pleural biopsy.However,the sensitivity and specificity of these methods in differentiating benign from malignant pleural effusion are not satisfactory.The objective of this study was to evaluate the diagnostic value of pleural fluid miR-21,miR-29c,and miR-182 in differentiating pleural effusions of varying oringin.Methods:1.Research object:A total of 126 patients with pleural effusions?65 cases of malignant pleural effusions and 61 cases of benign pleural effusions?were enrolled this study.2.Specimen processing:200 m L pleural fluid samples collected from each patient was placed in tubes containing anticoagulant?EDTA?,centrifuged for 1 hour.Then we sequentially extracted total RNA,transcribed reversely them into cDNA,and detect mi R-21,miR-29c,miR-182 by useing the fluorescence quantitative polymerase chain reaction?RT-PCR?.The relative expression levels of the microRNAs wrer calculated using the 2^-??Ct method.Pleural fluid CEA levels were measured simultaneously.3.Statistical analysis:Data are presented as median±SE.The diagnostic performance of each miRNA to distinguish malignant from benign pleural effusion was evaluated with the receiver operating characteristic?ROC?curve analysis.The optimum cut-off values were defined according to the ROC curves.The sensitivity,specificity,positive predictive value?PPV?,negative predictive value?NPV?,and accuracy for each miRNA were calculated according to the optimum cut-off values.The SPSS 21.0version statistical software was used for statistical analysis.Results:1.The expression levels of miR-21 and mi R-182 in malignant pleural effusion were significantly elevated as compared with those in benign pleural effusion specimens.The expression level of miR-29c in malignant pleural effusion specimens was decreased compared to that of benign pleural effusion specimens.2.The area under ROC curves of pleural fluid miR-21,miR-29c,and miR-182 for differentiating malignant from benign origin were 0.873?95%CI:0.808-0.939?,0.856?95%CI:0.790-0.920?,and 0.841?95%CI:0.772-0.911?respectively.The area under ROC curve of pleural fluid CEA?0.822;95%CI:0.703-0.873?was lower than those of the three miRNAs,although difference did not reach statistical significance.3.The sensitivity and specificity of pleural fluid miR-21,mi R-29c and miR-182 for diagnosing malignant pleural effusion were?83.1%and 85.2%?,?78.5%and 81.5%?and?83.1%and 73.4%?respectively,which were higher than those of pleural fluid CEA?75.4%and 71.2%?.4.Combination of pleural fluid mi R-21,miR-29c,miR-182,and CEA can increase the sensitivity,specificity,and accuracy in the diagnosis of malignant pleural effusion.Conclusions:miR-21,miR-29c and miR-182 might become valuable biomarkers in diagnosis of malignant pleural effusions.