Comprehensive Analysis Of Dysregulated LncRNAs And Their Competing Endogenous RNA Network In Stage Ⅰ Lung Adenocarcinoma

Objective: Long non-coding RNAs(lncRNAs)have been demonstrated to be an integral component of competing endogenous RNA(ceRNA)network.The purpose of this study was to explore the role of lncRNA-related ceRNA network in the development of stage I lung adenocarcinoma(LUAD),and screen the prognostic lncRNAs acting as ceRNAs.Methods: We collected 10 stage I LUAD patients’ tumor and adjacent normal tissue for RNA sequencing.The differentially expressed mRNAs,miRNAs and lncRNAs between tumor and corresponding normal tissues in stage I LUAD were obtained using the sequencing data.Accordingly,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,and the construction of lncRNArelated ceRNA regulatory networks were performed.Moreover,Weighted Gene Coexpression Network Analysis(WGCNA)was constructed using The Cancer Genome Atlas(TCGA)dataset.The quantitative real-time PCR assay was used to confirm the differential expression of the screened lncRNAs between tumor and adjacent normal tissue.Finally,Cox regression analysis was performed to reveal the potential effect of lncRNA identified on the recurrence of stage I LUAD.Results: A total of 1,955 DEmRNAs,165 DEmiRNAs and 1,107 DElncRNAs(fold change>2,P<0.05)were identified in theRNA sequencing profiles of 10 stage I LUAD patients.Of the 8,912 lncRNA-miRNA-mRNA regulatory networks constructed,LINC00639,RP4-676L2.1(also called LNCAROD)and FENDRR(fetal-lethal noncoding developmental regulatory RNA)were validated to be correlated with prognosis of stage I LUAD by WGCNA.The differential expression of which between tumor and adjacent normal tissue was confirmed by quantitative real-time PCR assay(P <0.001).Of these,FENDRR was associated with progression free survival(PFS)of stage I LUAD patients(Hazard Ratio [HR] 1.713,95% Confidence Interval [CI] 1.055-2.640,P<0.05)by Cox regression analysis.Further,it revealed that FENDRR,serving as a ceRNA,could bind to miR-6815-5p predicted by our dataset.Conclusions:(1)The expression level of FENDRR in stage I LUAD tissues was significantly lower than that in paracancer tissues,suggesting that FENDRR may regulate the expression of target mRNA by anchoring miR-6815-5p,and thus inhibit the progression of LUAD;(2)Patients with lower FENDRR expression level in stage I LUAD had significantly shorter PFS than patients with higher FENDRR expression level,suggesting that low expression of FENDRR may indicate poor prognosis of patients.