Bioinformatics Analysis Of MiRNA-218/FANCI Is Associated With Metastasis And Poor Prognosis In Lung Adenocarcinoma

ObjectiveBased on tumors microarray analysis,the key mRNAs and miRNAs related to the progression of lung adenocarcinoma were screened out,providing a theory basis for early diagnosis,therapeutic targets and prognosis evaluation of patients with lung adenocarcinoma.MethodsThe miRNA data set GSE63805,and mRNA microarray data sets GSE40791,GSE27262,GSE75037 were downloaded from Gene Expression Omnibus(GEO)database.The differentially expressed genes(DEGs)and differentially expressed microRNAs(DEMs)between LUAD tissues and normal lung tissue were obtained by using GEO2R,and overlapped DEGs were acquired with Venn Diagrams.Functional enrichment analysis of overlapped DEGs and DEMs was performed using the Database for Annotation,Visualization,and Integrated Discovery(DAVID)database and FunRich,respectively.Meanwhile,a protein-protein interaction(PPI)network was also employed to construct and visualize the interactions of overlapped DEGs by using the Search Tool for the Retrieval of Interacting Genes(STRING)and Cytoscape.Overall survival(OS)of DEMs were investigated by Kaplan-Meier plotter(KM plotter).We used the miRecords database to predict the targets of the DEMs,then visualized the DEM-DEG regulatory network with Cytoscape.To verify the relationship between FANCI and miR-218 expressions,TargetScan website was used.The expression of FANCI in LUAD samples and normal lung tissues was verified from GEO and Human Protein Atlas(HPA)databases.We also verified the FANCI expression using our own samples by RT-qPCR.Then,we used The Cancer Genome Atlas(TCGA)database to explore the relationship between the expression of FANCI and the clinicopathological characteristics and prognosis of LUAD patients.We analyzed the relationship between FANCI and immune infiltration in LUAD using the Tumor Immune Estimation Resource(TIMER)database.ResultsWe obtained 608 DEGs including 177 up-regulated and 431 down-regulated genes and 27 DEMs consisting of 16 up-regulated and 11 down-regulated miRNAs.9 DEMs were associated with poor OS for LUAD patients.26 overlapping genes and 30 miRNA-mRNA pairs were identified.FANCI was a hub gene and associated with poor OS.MiR-218 negatively regulates FANCI mRNA expressions.In the mRNA and protein level,FANCI expression was higher in LUAD tissues.The FANCI expression in LUAD was related to turmor size(χ2=13.96,p<0.001),lymphatic metastasis(χ2=3.88,p<0.05),distant metastasis(χ2=45.39,p<0.001)and stage(χ2=11.03,p<0.05).In addition,Cox regression analysis found that FANCI expression was an independent factor for predicting patients’ outcome(p<0.05),suggesting that FANCI may have utility as a prognostic biomarker in LUAD.Furthermore,the overall 5-year survival rates of the FANCI high and low expression groups were 32.6%and 38.7%(HR=1.611,95%CI=1.191-2.179,p=0.002),indicating that FANCI had an impact on overall survival for LUAD patients.The relationship between FANCI expression and B cell and neutrophil was weak in LUAD.FANCI could be considered as an independent prognostic marker in LUAD(p=0.039,HR=1.39,95%CI,1.02-1.89)by multivariate Cox regression analysis.ConclusionThese prognosis-related DEMs have provided potential biomarkers for LUAD diagnosis and treatment.miR-218 may negatively regulate FANCI,and FANCI could promote metastasis through ECM receptor interaction,leading to poor prognosis of lung adenocarcinoma.FANCI may be a key gene to determine metastasis and poor prognosis in patients with lung adenocarcinoma,which is expected to be a new target for molecular targeted therapy.The mechanism of FANCI leading to poor prognosis of lung adenocarcinoma may be related to immune microenvironment.