Application Of Plasma Exosomal MicroRNAs In Differentiating Benign And Malignant Solitary Pulmonary Nodules

Objective: With wide application of low-dose computed tomography(LDCT)in early lung cancer screening,solitary pulmonary nodule(SPN)are frequently detected.Due to their high etiological diversity and potential for malignancy,rapid and accurate identification and malignant SPN are crucial in the clinical management.Exosomal micro RNA(miRNA)expression is correlated with lung cancer proliferation,progression and metastasis,which makes it possible to be a biomarker for malignant SPN.The aim of this study was to explore the value of plasma exosomal miRNA in distinguishing benign or malignant SPN and detecting malignant SPN by studying their different expressions in patients with benign,malignant SPN and healthy control patients without SPN.Methods: Pre-treatment plasma exosomal miRNAs from 2 groups’ patients of malignant and benign SPN(4 cases each)were isolated and subjected for high-throughput sequencing,and candidate miRNAs were selected.Then,plasma levels of the candidate miRNAs in 48 malignant SPN,29 benign SPN and 14 healthy control patients without SPNs were detected by q PCR.Finally,diagnostic values of candidate miRNAs and were analyzed by AUROC analysis.Results: The expression level of plasma exosomal miR-1-3p and miR-125b-5p in malignant SPN group was lower than that in benign and healthy control group,while the plasma levels of miR-218-5p,miR-99a-5p and miR-9-5p in malignant SPNs were statistically higher than those in benign SPN.The sensitivity of 5 miRNAs as biomarkers in the identification of benign and malignant SPNs was 87.5%,89.6%,72.9%,75.0% and 62.5%,the specificity was 55.2%,100%,89.7%,79.3% and 75.9%,respectively.The sensitivity and specificity of miR-1-3p combined with miR-99a-5p in the diagnosis of malignant SPN can both reach to 100%.The sensitivity of 5 miRNA as biomarkers in differentiating malignant SPN and healthy people(benign SPN and healthy control group)was 83.3%,89.6%,72.9%,75.0% and 62.5%,and the specificity was 51.2%,95.3%,90.7%,86.0% and 81.4%,respectively;the sensitivity and specificity of miR-1-3p,miR-99a-5p and miR-125b-5p(or miR-218-5p)combined in the diagnosis of malignant SPN can also reach to 100%.Conclusion: The expression of plasma exosomal miR-125b-5p,miR-1-3p,miR-218-5p,miR-99a-5p and miR-9-5p was statistically different between patients with benign or malignant pulmonary nodules.Those miRNAs have relatively high sensitivity and specificity for the diagnosis of malignant SPN.