Abstract
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.
Highlights
Phosphatase and tensin homolog on chromosome 10q23 (PTEN) mutations have been reported to be involved in the development and prognosis of endometrial carcinoma (EC)
The K-M curves revealed that the EC patients with PTEN mutation (PTEN mut) exhibited a longer survival time than the patients with wild-type PTEN (PTEN wild; P < 0:001; Figure 2(b)), and the percentage chart shows that the PTEN mutation occurred more frequently in the younger patients with a lower stage and grade of cancer (P < 0:001; Figures 2(c)–2(e))
Considering the robust prognostic value of PTEN mutational status, we developed a PTEN mutational status-associated prognostic signature to predict the prognosis of EC
Summary
PTEN mutations have been reported to be involved in the development and prognosis of endometrial carcinoma (EC). A prognostic gene signature associated with PTEN mutational status has not yet been developed. We generated a PTEN mutation-associated prognostic gene signature for EC. 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 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. The PTEN mutationassociated prognostic gene signature that we developed could be used as a favorable prognostic biomarker for EC. 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. Investigators [6] have demonstrated that PTENdeficient endometrial epithelial cells were more likely to convert to complex atypical hyperplasia in response to estrogen stimulation and develop into EC; and, PTEN deficiency is generally considered to be an early event
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