Differential Expression And Clinical Significance Of Smoking-related Lung Adenocarcinoma Gene Expression Based On TCGA Database

OBJECTIVE: We explored the effect of smoking on the expression of RNA and microRNAs in lung adenocarcinoma patients,and obtained the related genes and microRNAs closely related to survival.We further explored the clinical value of smoking in guiding the diagnosis,treatment and prognosis of lung adenocarcinoma.METHODS: In this study,TCGA database was used to obtain the data of the expression profiles of RNA and microRNAs in lung adenocarcinoma samples and the data related to clinical prognosis.The samples with complete smoking and prognosis information were screened for further analysis.(1)We used limma package in R language statistical software to analyze the differences in the expression data of mRNA,and obtained the differentially expressed genes related to smoking.The screening conditions were set as P.Value<0.001,adj.P.Val<0.001,logFC>2.Kaplan-Meier survival analysis of differentially screened genes was performed by SPSS 20.0 software.P< 0.05 showed that the expression of differentially screened genes in lung adenocarcinoma had a significant impact on the survival of patients.DAVID software was used to explore the KEGG_PATHWAY signaling pathway in differentially expressed genes of smokingrelated lung adenocarcinoma,which had significant effects on survival.(2)We also used the limma package of R language to analyze the differentially expressed microRNAs in smoking and non-smoking samples.The screening conditions were P.Value<0.05,adj.P.Val<0.06,logFC>2.Further,we used SPSS 20.0 software to analyze the KaplanMeier survival of differentially expressed microRNAs when P<0.05 showed that the expression of microRNAs in lung adenocarcinoma was correct.The survival time of patients was significantly affected.RESULT:1.By using the limma package of R language statistical software,we analyzed and screened the data of 40 differentially expressed genes.Two of them,HDGF and PRO1741,were up-regulated in smoking lung adenocarcinoma tissues,while the remaining 38 differentially expressed genes were down-regulated.2.By using the Kaplan-Meier model of SPSS20.0 software,we analyzed the survival of 40 differentially expressed mRNAs and got 10 statistically significant ones,namely CPQ(P=0.029),CLEC4F(P=0.021),FAM13B(P=0.045),DIO1(P=0.006),RPS6KA1(P=0.003),CD74(P=0.002),HLA-DMA(P=0.003),CLUL1(P=0.028),TM4SF8(P=0.028)and FUCA1(P=0.005).These 10 lung adenocarcinomas expressed down-regulated mRNA in smoking tissues,and increased expression increased survival time of lung adenocarcinoma patients.3.The KEGG_PATHWAY pathway of 10 differentially expressed surviving genes was analyzed by using DAVID 6.8.The results showed that five of them existed in known signaling pathways,including CD74,DIO1,FUCA1,HLA-DMA and RPS6KA1.4.We analyzed and screened the data of microRNAs by using the limma package of R language software.A total of 19 differentially expressed microRNAs were obtained,which were down-regulated in smoking lung adenocarcinoma tissues.5.After survival analysis of 19 differentially expressed microRNAs by Kaplan-Meier model,we obtained 8 microRNAs with statistical significance,including hsa-mir-4709(P=0.001),hsa-mir-99a(P=0.019),hsa-mir-30e(P=0.002),hsa-mir-1976(P=0.015),hsa-mir-181c(P=0.002),hsa-mir-101-2(P=0.001),hsa-mir-101-1(P=0.001)and hsa-let-7c(P=0.043).These eight down-regulated microRNAs were expressed in smoking lung adenocarcinoma tissues.Increased expression of microRNAs increased survival time of lung adenocarcinoma patients.CONCLUSION: This study compared the lung adenocarcinoma tissues of smokers and non-smokers.It was found that there were 10 down-regulated differentially expressed genes and 8 down-regulated differentially expressed microRNAs in the lung adenocarcinoma tissues of smokers.Increased expression of these differentially expressed microRNAs would improve the survival time of lung adenocarcinoma patients,provide guidance for gene diagnosis of lung adenocarcinoma patients,provide guidance for precise individualized treatment and improve lung adenocarcinoma patients.The prognosis of the patients has important clinical significance.