Construction Of A Mitotic Cell Cycle-related Prognostic Nomogram For Lung Adenocarcinoma

Objective:This study aimed to construct a prognosis-related Nomogram prediction model based on the differences in transcriptome sequencing data and clinicopathological features between patients with early-stage lung adenocarcinoma(LUAD)and those with mid-late-stage LUAD and to explore the relevant biological functions.Methods:This study downloaded clinicopathological and transcriptome sequencing data of LUAD patients from The Cancer Genome Atlas(TCGA)and the Gene Expression Omnibus(GEO)databases and enrolled 866 patients by establishing inclusion and exclusion criteria.Differentially expressed genes were compared and screened between early-stage LUAD and mid-late-stage LUAD,from which genes with independent prognostic value were screened by univariate COX analysis.Using LASSO-COX regression analysis,we constructed a risk signature and divided patients into high-risk and low-risk groups based on the median risk score.Kaplan-Meier(K-M)curves and receiver operating characteristic(ROC)curves were plotted in the training and validation groups,respectively,and using the area under the curve(AUC)validate the performance of the risk signature.Then,to make a prediction model with higher accuracy,we constructed a nomogram prediction model for predicting 1-and 3-year survival of LUAD patients by incorporating staging,epidermal growth factor receptor(EGFR)mutation status,and risk signature.The accuracy was verified by the Calibration plot and the concordance index(C-index).Then,relevant biological functions were explored and validated by Gene Ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis,Gene Set Variation Analysis(GSVA),and Gene Set Enrichment Analysis(GSEA).Results:First,differential analysis exhibited 74 differentially expressed genes(34 genes up-regulated and 40 genes down-regulated).The results of univariate COX analysis showed that 28 of these genes had independent prognostic values.Second,a 13-gene risk signature was constructed by LASSO-COX regression analysis,which was associated with the overall survival of LUAD patients.The results of the K-M analysis showed significant differences in prognosis between the high-risk and low-risk groups(P<0.0001).Then,biological functional analysis revealed that the signature was related to the mitotic cell cycle.Finally,a nomogram was developed based on the risk signature and clinicopathological characteristics.The nomogram showed reliable predictive ability in both the training and validation groups.Conclusion:The novel mitotic cell cycle-related nomogram prediction model can accurately predict the prognosis of lung adenocarcinoma patients and is helpful for individualized clinical application.