Alteration Of LncRNAs In Lung Squamous Carcinoma And Lung Adenocarcinoma And Its Clinical Significance

Aims To investigate the alteration of long non-coding RNA in lung squamous carcinoma and lung adenocarcinoma.To determine the effect of sex,age,race,smoking and stage on IncRNA.To find out the IncRNAs that could help predict overall survival in lung squamous carcinoma and lung adenocarcinoma.To illustrate the mechanism how lncRNAs are regulted.Methods We took advantage of The Cancer Genome Atlas(TCGA)and cBioPortal to analyze the alteration of IncRNAs in lung squamous carcinoma and lung adenocarcinoma.We downloaded clinical and genomic data from TCGA database,and found out lncRNAs with high alterations with SPSS software analysis.We used lncRNA2Function to analyze GO and pathway of these identified IncRNAs.We analyzed the coexpressed gene list and predicted the role of lncRNAs in lung squamous carcinoma and lung adenocarcinoma.For these highly expressed IncRNAs,we took advantage of Chip-seq data from ENCODE,genomic conservation analysis and CpG islands,and used the dual luciferase system to illustrate the mechanism how IncRNAs are regulated.Results In LUSC,624 lncRNAs had alteration rates>1%and 64>10%.In LUAD 625 lncRNAs had alteration rates>1%and 36>10%.Among those,620 lncRNAs had alteration frequencies>1%in both LUSC and LUAD,while 22 were LUSC-specific and 23 were LUAD-specific.Twenty IncRNAs had alteration frequencies>10%in both LUSC and LUAD,while 44 were LUSC-specific and 16 were LUAD-specific.In LUSC,22 lncRNAs were in one cytoband(chr 3:p26.3),while there were no such accumulation in LUAD.GO and pathway analysis showed that top five moleculare functions of lncRNAs in LUSC and LUAD are common.Only Retinoic acid receptor binding was enriched in both LUSC and LUAD.And the top ten biologial function were the same in LUSC and LUAD.Two lncRNAs(IGF2BP2-AS1 and DGCR5)correlated with better OS in LUSC,and three(MIR31HG,CDKN2A-AS1 and LINC01600)predicted poor OS in LUAD.The combination of IGF2BP2-AS1 and DGCR5 could improve prediction power in LUSC,while the combination of CDKN2A-AS1?MIR31HG and LINC01600 could improve survival prediction in LUAD.In LUSC,alteration frequence of SNHG11 and LINC00662 are higher in male than in female.In LUAD,alteration frequence of CASC8 was higher in male than in female.In LUSC,LINC00888,LINC00501,LINC00578,DUBR,LINC00879,DGCR5,SNHG10,LINC01192,SNHG15,LINC00634,LINC00880,LINC00636,LINC00881,LINC00901,DANCR,BAALC-AS2,PVT1,CASC8,LINC00603,MIR205HG,FAM167A-AS1,and LINC00937 might be involved in age related pathogenesis of LUSC.In LUAD,LINC00609,PTCSC3,LINC00517,SNHG20,LINC00957,SNHG17,LINC00265,SNHG15,ZFAS1,SNHG6,PVT1,HAR1A,IGF2BP2-AS1,MIR205HG,BAALC-AS2,LINC01600,and CASC8 might be involved in age related pathogenesis of LUAD.In LUSC,PVT1,MIR205HG,SNHG17,CECR7,LINC00923,HCG18 were with obvious differences between black and white.In LUAD,EXOC3-AS1,PVT1,LINC00467,LINC01194,LINC0095,LINC002657,SNHG17 were with obvious differences between black and white.In LUSC,LOH12CR2?DANCR?DANCR?HPYRI?FAM66C?DGCR5?LINC00636?LINC00901?DANCR?SNHG17?LINC00879?FAM66C?DGCR5?LINC00901?FAM66C?SNHG10?SNHG17 played important roles in smoking induced cancer pathogenesis.In LUAD,HAR1A?TP53TG1?IGF2BP2-AS1?EXOC3-AS1?LINC00603?CASC8?LINC01600?LINC00626?LINC00894?PVT1?HPYR1 played important roles in smoking induced cancer pathogenesis.In LUSC,CDKN2A-AS1,GAS5,FAM74A3,DANCR,LINC01565,SNHG20,SNHG10,LINC00923,SNHG6,LINC00626 ? BAALC-AS2 were differently altered in different stages.In LUAD,EXOC3-AS1,MIR31HG,LINC00609,PTCSC3,LINC00626,LINC00517,SNHG6,LINC00467,MIR31HG,CASC8,ZFAS1 and MIR205HG were differently altered in different stages.Alteration of IGF2BP2-AS1?DGCR5?and LINC01600 were due to upregulation.Chip-seq and luciferase reporter assays identified potential IGF2BP2-AS1,DGCR5 and LINC01600 promoters and enhancers.Conclusions LncRNAs were altered in both LUSC and LUAD.There were both some common characters and some variances.The role of IncRNAs in LUSC and LUAD were illustrated by analyzing GO and pathways of these altered lncRNAs.Sex,age,race,smokinng and stages could affect alteration of IncRNAs.LncRNAs that could predict overall sruvival were identified.The function of these identified IncRNAs in lung cancer were predicted by analyzing the GO and pathway of the coexpressed genes.LncRNAs could be regulated through promoters and enhancers.