Construction and validation of a prognostic model for predicting lung adenocarcinoma based on mitochondrial metabolism relat-ed-genes
Objective To construct and validate a prognostic model of lung adenocarcinoma(LUAD)based on mitochondrial metabolism related-genes(MMRGs)and to explore its clinical significance.Methods The LUAD cohort was obtained from The Cancer Genome Atlas(TCGA)and randomly divided into training and validation sets by 7:3.The MMRGs specifically expressed in LUAD were obtained,and then the prognosis-related MMRGs were screened by Cox and LASSO regression in the training set to construct the prognostic model.The risk scores were calculated,and the patients were categorized into low-risk and high-risk groups by their median values.Kaplan-Meier curves and ROC were plotted in the training set,validation set,entire set of TCGA and three test sets,including GSE30219,GSE41271 and GSE68465,respectively to observe the robustness of the model.Cox regression analysis was applied to observe the performance and robustness of the prognostic model.A nomogram model was constructed to further explore the prognostic efficacy combining risk score and other independent prognostic factors.The correlation between prognostic models and patients'clinical features,driver gene mutations,and immune infiltration was explored.Results A prognostic model consisting of four MMRGs was constructed.Survival analysis showed that the prognosis of patients in the high-risk group was significantly worse than that of patients in the low-risk group,and multivariate Cox regression analysis indicated that risk score could be an independent factor for the prognosis of patients with LUAD.The nomogram involved age,T stage,N stage and risk score was able to more accurately predict the prognosis of patients.Risk score of patients increased with increasing T stage,N stage and TNM stage,which was higher in smoking or kirsten rats arcomaviral oncogene homolog(KRAS)mutation patients compared with that of non-smoking and KRAS wild type patients,but lower in epidermal growth factor receptor(EGFR)mutation patients compared with that of EGFR wild type patients.The infiltration degree of activated mast cells,activated CD4 memory T cells,neutrophils,unactivated nature killer cells,plasma cells,M1 macrophages and M0 macrophages was high among patients in the high-risk group.Conclusion The prognostic model constructed based on MMRGs has good accuracy and stability in predicting the prognosis of patients with LUAD,and is closely related to the malignant phenotypes of the patients,the mutations of the driver genes mutations,and immune infiltration,which could potentially provide a basis for the treatment of LUAD and the assessment of prognosis.
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