Significance of TP53 Mutational Status-Associated Signature in the Progression and Prognosis of Endometrial Carcinoma

Abstract

Background. TP53 mutations are associated with poor outcome for patients with endometrial carcinoma (EC). However, to date, there have been no studies focused on the construction of TP53 mutational status-associated signature in EC. In this study, we aim to conduct a TP53 mutation-associated prognostic gene signature for EC. Methods. Hence, we explored the mutational landscape of TP53 in patients with EC based on the simple nucleotide variation data downloaded from The Cancer Genome Atlas (TCGA) database. Differential expression analysis and least absolute shrinkage and selection operator (LASSO)-Cox analysis was used to establish TP53 mutation-associated prognostic gene signature. The overall survival rate between the high-risk and low-risk groups was compared by the Kaplan-Meier (K-M) method. Results. We found that the TP53 mutation was associated with poor outcome, older age, lower BMI, and higher grade and stage of EC in patients. A TP53 mutational status-associated signature was established based on transcriptome profiling data. Moreover, the patients in TCGA database were categorized into high- and low-risk groups. Kaplan-Meier (K-M) analysis indicated that the patients in the high-risk group have poor survival outcome. Furthermore, receiver operating characteristic (ROC) curves confirmed the robust prognostic prediction efficiency of the TP53 mutational status-associated signature. Finally, the prognostic ability was successfully verified in the other two datasets from cBioPortal database as well as in 60 clinical specimens. Univariate (hazard ratio HR=1.041, 95%CI=1.031-1.051, p<0.001) and multivariate (hazard ratio HR=1.029, 95%CI=1.018-1.040, p<0.001) Cox regression analyses indicated that the TP53 mutational status-associated signature could be used as an independent prognostic factor for EC patients. Conclusion. In summary, our research constructed a powerful TP53 mutational status-associated signature that could be a potential novel prognostic biomarker and therapeutic target for EC.