Construction And Evaluation Of A Prognostic Model For Lung Adenocarcinoma Based On Chromatin Regulators-Related Long Non-Coding RNA

Objective:By constructing a prognostic model of Chromatin regulators(CRs)related long non-coding RNA(lncRNA)in lung adenocarcinoma(LUAD),To study the predictive performance of the prognostic model and its relationship with the clinical characteristics of patients with lung adenocarcinoma,and to explore the regulatory mechanism of chromatin regulatory factors in LUAD,so as to provide a new way for the treatment and individualized management of lung adenocarcinoma.Materials and Methods:LUAD transcriptome data,LUAD clinical data and LUAD mutation data were downloaded from The Cancer Genome Atlas(TCGA)database and processed in a series.According to relevant literature,870 CRs-related genes were found.The "limma" software package was used to intersected LUAD-related lncrnas and obtain 704CRS-related lncrnas.The total sample data were randomly divided into training set and test set.Univariate Cox regression analysis,least absolute shrinkage and selection operator penalty(LASSO)analysis and multivariate Cox regression analysis were performed on the training set,and then 11 CRs-related lncrnas were screened out to construct a prognostic model.The risk score of the prognostic model was then calculated using the formula for calculating the risk score.The training set,test set and the all set were divided into high and low risk groups,and then survival analysis,progression-free survival analysis,independent prognostic analysis,principal component analysis,tumor mutation analysis,nomogram and consistency curve were performed to evaluate the predictive ability of the model and the ability to distinguish between high and low risk groups.Pathway enrichment analysis,immune function differential analysis,immunotherapy and drug sensitivity prediction of the differential genes were performed,and a series of features of the model were identified.Finally,the expression of LINC00707,LINC01503,LINC02454 and TBX5-AS1 was analyzed by heat map and Quantitative real-time PCR.qRT-PCR was used to detect its expression in tumor tissues and normal tissues.Results:1.Through univariate COX regression analysis,LASSO regression analysis and multivariate COX regression analysis,Eleven chromatin regulatory factors related lncrnas(LINC01503,LINC00621,LINC02454,ITFG2-AS1,FRMD6-AS1,LINC00578,LINC01415,TBX5-AS1,ZNF516-DT,L3MBTL2-AS1,LINC00707 and LINC01415)were established.2.The survival analysis of the prognosis of the three cohorts in the training set,test set and the whole set showed that the prognosis of the high-risk group was worse than that of the low-risk group.The scatter plot of prognostic survival status showed that the survival time of the high-risk group was shorter and the number of deaths was higher.Univariate and multivariate COX regression analysis showed that risk score(P<0.05)can be used as an independent prognostic factor for LUAD.The consistency curve and nomogram showed that the risk model had relatively accurate prediction ability.Both PFS analysis and PCA analysis showed that the risk model could well distinguish between high and low risk groups.The above results indicate that the model has good and stable predictive ability.When tumor immune dysfunction and exclusion(TIDE)score analysis was performed,we found that the high-risk group had a lower TIDE score,and the TIDE score was statistically significant(P< 0.05),indicating that the immune escape ability of the high-risk group was weak,and its immunotherapy effect was better than that of the low-risk group.Drug sensitivity analysis showed that the high-risk group was more sensitive to commonly used chemotherapy drugs and could be better used to guide the treatment.3.TCGA heat map and qRT-PCR showed that the expression levels of LINC00707,LINC01503 and LINC02454 in lung cancer tissues were significantly higher than those in normal tissues,while TBX5-AS1 was opposite.Conclusions:The prognostic models of 11 CRs-related lncrnas related to the prognosis of LUAD were constructed.A series of experiments confirmed that our risk model had good predictive ability.The related lncrnas are of certain significance for the study of the development mechanism and prognosis of LUAD.Through functional enrichment analysis,it was found that the enriched pathways of the differential genes may be related to the development mechanism of cancer.The differential analysis of immune function showed that the differential genes were related to tumor immunity.Immunotherapy analysis and drug sensitivity analysis provide reference value for the treatment and prognosis of LUAD.LINC00707,LINC01503,LINC02454 and TBX5-AS1 may be associated with the development of lung cancer.