Significance of a PTEN Mutational Status-Associated Gene Signature in the Progression and Prognosis of Endometrial Carcinoma

BACKGROUND: PTEN mutations have been reported to be involved in the development and prognosis of endometrial carcinoma (EC). However, a prognostic gene signature associated with PTEN mutational status has not yet been developed. In this study, we generated a PTEN mutation-associated prognostic gene signature for EC. METHODS: We obtained the single-nucleotide variation and transcriptomic profiling data from The Cancer Genome Atlas database as training data and implemented the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm to establish a PTEN mutation-associated prognostic gene signature. The overall survival rates of the high-risk and low-risk groups were determined with the Kaplan-Meier (K-M) method, and the accuracy of risk score prediction was tested by using the receiver operating characteristic (ROC) curve. RESULTS: The K-M curves revealed that the EC patients with PTEN mutations augured favorable survival outcomes. Differential expression analysis between the EC patients with PTEN mutation and wild-type PTEN identified 224 differentially expressed genes (DEGs). Eighty-four DEGs that manifested prognostic value were fitted into the LASSO-Cox analysis, and a PTEN gene signature with seven mutation-associated prognostic genes that showed robust prognostic ability was constructed; this signature was then successfully validated in the other two datasets from the cBioPortal database as well as with 60 clinical specimens. Furthermore, the PTEN mutation-associated prognostic gene signature proved to be an independent prognostic predictor of EC. Remarkably, the EC patients in the high-risk group were characterized by higher tumor stages and grades as well as lower tumor mutation burden with respect to EC, with a poor survival outcome. Collectively, the PTEN mutation-associated prognostic gene signature that we developed could now be used as a favorable prognostic biomarker for EC. CONCLUSION: In summary, we developed and validated a prognostic predictor for EC associated with PTEN mutational status that may be used as a favorable prognostic biomarker and therapeutic target for EC.