Establishment of tumor protein p53 mutation-based prognostic signatures for acute myeloid leukemia

The tumor protein p53 gene (TP53) mutations are associated with poor prognosis of patients with acute myeloid leukemia (AML). This study aimed to establish TP53 mutation-based prognostic risk signatures.

The transcriptomes and clinical characteristics of AML patients were acquired from The Cancer Genome Atlas database, including 11 TP53-mutant samples and 114 TP53-wildtype samples. Differentially expressed mRNAs and long non-coding RNAs (lncRNA) in TP53-mutant samples were identified. Weighted gene correlation network analysis was performed to generate survival-associated co-expression modules. LASSO regression analysis was conducted to build mRNA- and lncRNA-based prognostic risk signatures. Kaplan-Meier curve analysis and multivariate regression analysis were carried out to assess the prognostic values of the risk signatures. Receiver operating characteristic (ROC) analysis was performed to evaluate the accuracy of the signatures.

Based on the co-expression modules, a 5-mRNA risk signature and a 13-lncRNA risk signature were constructed to predict the overall survival for AML patients. Kaplan-Meier curves revealed that the high-risk patients had significantly shorter overall survival than the low-risk patients. ROC analysis yielded 1-, 3-, and 5-year AUCs of 0.681, 0.783, and 0.827 for mRNA signature and 0.85, 0.835, and 0.908 for lncRNA signature. Multivariate regression analysis revealed that both mRNA (HR = 1.45, P< 0.001) and lncRNA (HR = 1.19, P< 0.001) risk scores were independent prognostic factors for AML patients.

We provided a potential patients stratification tool for AML prognosis prediction and management, which established by effective TP53 mutation-related gene signatures.