Bioinformatics Screening Of MicroRNA Biomarkers In Lung Adenocarcinoma

BACKGROUND:Lung cancer is one of the highest incidence rate of malignant tumors in the world,and it is also the most malignant tumor.In terms of incidence rate,it ranks the second in the United States.Lung adenocarcinoma is one of the most common histological subtypes of NSCLC.The early symptoms of lung cancer are hidden and hard to find.Up to now,the early diagnosis of lung cancer is still difficult to some extent.According to statistics,80%of lung cancer patients have been diagnosed as advanced for the first time and cannot be treated by surgery.In the precise treatment of lung cancer,the molecular mechanism of its pathogenesis,progress and drug resistance is a hot research topic,and it is also the key to drug treatment of lung cancer.The screening of biomarkers is very important for the accurate early diagnosis and treatment of lung cancer.METHODS:In our integrated analysis,the data contains gene expression data from miRNA,mRNA and human lung adenocarcinoma with reference to miRNA-mRNA networks.First of all,we need to collect data and reconstruct the lung adenocarcinoma specific network,and then recognize miRNA biomarkers according to the network structure and biological function.Then,the selected miRNA needs to verify the correlation of lung adenocarcinoma through literature mining,confirmation and bioinformatics.The gene expression and miRNA expression data of lung adenocarcinoma were extracted from the open GEO database,and the data set was GSE63459 and GSE36681.To standardize the data,the linear model in limma R package was used to select the differentially expressed mRNA.The empirical Bayes parameter method is applied to the calculation of P value and other parameters.The Benjamini-Hochberg correction method is used to adjust the p value.The adjustment value is less than 0.05 is considered to be significant.Model construction,verification and identification of miRNA biomarkers for lung adenocarcinoma.From December 2018 to February 2019,35 patients with primary lung adenocarcinoma were selected from respiratory department and thoracic surgery department of Shandong Provincial Hospital Affiliated to Shandong University.In the control group,26 healthy volunteers were recruited.Peripheral blood samples were collected at 10 ml for each subject,and the microRNAs level was detected by QRT PCR.TCGA database was used to investigate the differential expression of microRNAs and its effect on prognosis.RESULTS:The miRNA biomarkers for the diagnosis and prognosis of lung adenocarcinoma were reported in the PubMed citation.Most of the miRNA are characterized by high NOGs and TFPs.Firstly,93 miRNAs and 331 genes were detected.The Wilcoxon symbol rank test screened 9 miRNAs,and the p value was less than 0.05.The screening of 9 miRNAs may be biomarkers that can be used to predict lung adenocarcinoma.Among the nine predicted miRNAs,four(mir-145-5p,mir-182-5p,mir-141-3p and mir-590-3p)were reported as biomarkers,and the remaining five(mir-204-5p)mir-567,mir-454-3p,mir-338-3p and mir-139-5p)were recommended as new biomarkers for diagnosis of lung adenocarcinoma.Further functional enrichment analysis was carried out.Finally,we detected five new miRNA biomarkers,including miR-204-5p,miR-567,miR-454-3p,miR-338-3p and miR-139-5p.The level of screened microRNAs was detected by qRT-PCR.The results showed that the expression levels of microRNAs in lung adenocarcinoma group were significantly higher than those in control group,and AUCs of ROC curves were higher than CEA and CA125.TCGA data analysis showed that all screened microRNAs had no definite correlation with prognosis and survival time of lung adenocarcinoma patients.CONCLUSIONS:Bioinformatics found that miR-204-5p,miR-454-3p,miR-338-3p and miR-139-5p can be used as a biomarker in the diagnosis of lung adenocarcinoma.These findings are worthy of further experimental verification in the future clinical application.