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

Abstract BackgroundPTEN mutation had been reported to be involved in the development and prognosis of endometrial carcinoma (EC). However, a prognostic genes signature associated with PTEN mutational status has not been developed. In this study, we aim to conduct a PTEN mutation associated prognostic genes signature for EC.MethodsWe obtained the simple nucleotide variation and transcriptome profiling data from The Cancer Genome Atlas database as training data. Lasso Cox regression algorithm was used to establish PTEN mutation associated prognostic genes signature. The overall survival rate of the high-risk and low-risk groups was determined by Kaplan-Meier (K-M) method. The accuracy of risk score prediction was tested by ROC curve.ResultsK-M curves revealed that the EC patients with PTEN mutation have favorable survival outcome. Differential expression analysis between the EC patients with PTEN mutation and PTEN wild identified 224 differential expression genes (DEGs). Eighty-four DEGs with prognostic value was fitted into least absolute shrinkage and selection operator (LASSO)–Cox analysis and a seven PTEN mutation associated prognostic genes signature with robust prognostic ability was constructed, which was successfully validated in the other two datasets from cBioPortal database as well as 60 clinical specimens. Furthermore, the PTEN mutation associated prognostic genes signature had been proved to be an independent prognostic predictor for EC. Remarkably, the EC patients in high-risk group were characterized with higher stages and grades as well as lower tumor mutation burden of EC, with poor survival outcome. Collectively, the PTEN mutation associated prognostic genes signature was a favorable prognostic biomarker for EC.ConclusionIn summary, we conducted and validated a prognostic predictor for EC associated with PTEN mutational status, which may be used as favorable prognostic biomarkers and therapeutic targets for EC.