Identification Of Key MRNAs And Key LncRNAs In Nasopharyngeal Carcinoma And Bioinformatics Analysis Of Their Regulatory Pathways

Objective: Bioinformatics analysis and gene chip technology were used to identify key mRNAs and key LncRNAs associated with Nasopharyngeal carcinoma(NPC),and to investigate the molecular regulation mechanism of key mRNAs in the occurrence and progression of NPC.Methods: 1)Screening and downloading data sets from the Comprehensive Gene Expression Database(GEO)according to inclusion criteria;2)The differential expression of mRNAs and LncRNAs in the GSE95166 dataset after quality control was analyzed by Limma R packet,which were named as differential mRNAs(DEGs)and differential LncRNAs(DELS),respectively.3)Weighted gene co-expression network analysis(WGCNA)was performed on the expression profile of GSE40290 dataset using WGCNA R packet.4)The genes in the key modules of DEGS and WGCNA were overlapped by R Venny package,and the overlapped common genes were regarded as intersection mRNAs;5)The selected DELS and intersection mRNAs were matched in Enco RI database to obtain targeted mRNAs of DELS,which were regarded as key DELS and key DEGs;6)Online analysis tool UCSC was used to construct the corresponding relationship of nasopharyngeal carcinoma LncRNA-miRNA-mRNA and its gene mapping on the chromosome;7)Gene ontology(GO)analysis and pathway enrichment(KEGG)analysis of key genes were conducted through online analysis website David and R language.Results: 1)Based on screening criteria,nasopharyngeal carcinoma microarray expression profile dataset GSE40290 and GSE95166 were obtained from GEO database,including 29 nasopharyngeal carcinoma tissue samples and 12 nasopharyngeal normal tissue samples.2)A total of3758 DEGs and 408 DELS were identified in the GSE95166 dataset.There were 1871 up-regulated genes and 1887 down-regulated genes in DEGs,255 up-regulated genes and 153 down-regulated genes in DELS.3)A total of 13,063 genes with gene symbol were found in the data set GSE40290,and 3401 genes in the top 25% of variance were selected for WGCNA analysis.A total of 14 gene modules related to sample tissues were obtained,among which 6 were significantly positive related risk modules for nasopharyngeal carcinoma.4)62 genes in the yellow-green modules with the highest positive correlation with nasopharyngeal carcinoma analyzed by WGCNA were intersected with DEGs,and 20 intersection mRNAs were obtained.5)A total of 186 key DELS and 16 key DEGs were matched in Encori database.Among them,there were 5DEGs with difference multiples greater than 2,that is,up-regulated DEGs:FXYD3 and SOX2,down-regulated DEGs:PLAU,GJA1 and CLDN1.6)The most gene localizations of key DELS and key GGs on human chromosomes were on chromosome 3,and there was no differential gene recombination localization on Y chromosome.7)GO analysis showed that 16 key DEGs were mainly concentrated in hyaluronan biosynthesis,bone mineralization,regulation of intercellular tight junction components,adhesion plaque kinase and cell matrix adhesion(p-value<0.05);8)KEGG analysis showed that 16 key DEGs were mainly concentrated in arrhythmogenic right ventricular cardiomyopathy,ECM-receptor interaction,PI3K-Akt signaling pathway,adhesion plaque and corrosion resistance.Conclusion: Studies have shown that 16 key mRNAs and 186 key lncRNAs may be involved in the pathogenesis and regulation of nasopharyngeal carcinoma,among which SOX2,FXYD3,GJA1,PLAU and CLDN1 are closely related to the pathogenesis of nasopharyngeal carcinoma,and their potential as tumor markers of nasopharyngeal carcinoma need further experimental verification.