Screening Of LncRNA Related To Prognosis Of Colon Cancer Based On TCGA Database And Establishment Of Prognostic Risk Mode

BackgroundColon cancer is common tumor of digestive system.With the diet structure changing to high fat,high protein and low fiber,colon cancer is on the rise.At present,the prognosis of colon cancer patients mainly depends on TNM stage.In serological examination,CEA,CA19-9 and other biomarkers play an important role in prognosis evaluation,but their sensitivity and specificity are not up to the mark.New biomarkers and prognostic assessment models are urgently needed to improve the accuracy of diagnosis and treatment for colon cancer patients.ObjectiveBased on the TCGA database,bioinformatics technology was used to analyze the expression data of colon cancer.Then we screen lncRNAs associated with the prognosis of colon cancer,and build a prognostic risk model.MethodTranscriptome data of colon cancer were downloaded and sorted from TCGA,then we constructed an expression matrix of lncRNA about paired samples.Differentially expressed lncRNAs(delncRNAs)were obtained by R-packet "edgeR".For delncRNAs,univariate COX regression analysis,Lasso analysis,Kaplan-Meier(K-M)survival analysis and multivariate COX regression analysis were performed to obtain the prognostic associated lncRNAs.The prognostic risk model of colon cancer was established based on the coefficient of multivariate COX regression model.Then we evaluated the accuracy through C-index value,time-dependent receiver operating characteristic(ROC)curve,area under ROC curve(AUC)value,and K-M survival analysis.CeRNA network was constructed for the lncRNAs in our model.GO and KEGG analysis were performed for related mRNAs to explore the mechanism of lncRNA affecting the progression of colon cancer.Results5460 lncRNAs were screened by arranging the transcriptome data.868 delncRNAs were obtained by paired-sample analysis,including 548 up-regulated genes and 320 down-regulated genes.After univariate COX regression analysis,40 lncRNAs were obtained.Through lasso regression analysis,we got 34 lncRNAs.14 lncRNAs remained after K-M survival analysis.Multivariate COX regression analysis revealed 7 prognostic related lncRNAs(down-regulated genes:LINC01132;up-regulated genes:ELFN1-AS 1,RP5-884M6.1,LINC00461,RP1-79C4.4,RP4-816N1.7,RP3-380B8.4).The prognostic assessment model was constructed according to the coefficient.The C-index of the model value was 0.82;the AUC values at 3 and 5 years were 0.79 and 0.84;K-M survival analysis showed a significant difference in survival rate between high and low risk groups(P<0.0001).Next,we constructed the ceRNA network,the KEGG enrichment analysis suggested that the down-regulation lncRNA inhibit the progression of colon cancer possibly through the pathways of Regulation of actin cytoskeleton,Proteoglycans in cancer and PI3K-Akt signaling pathway;up-regulation lncRNAs promote colon cancer possibly through the pathways of Cellular adhesion molecules,Focal adhesions and Phagosomes..ConclusionIn our study,we constructed a prognostic risk model of colon cancer with 7 lncRNAs,which has a nice accuracy in predicting the survival prognosis of colon cancer patients.Each lncRNA is a potential independent prognostic biomarker.The prognostic risk model has certain value for clinical prognostic assessment of colon cancer patients.