Autophagy-related risk signature based on CDNK2A to facilitate survival prediction of patients with endometrial cancer

Background: Autophagy plays an important role in immunity and inflammation. The present study aimed to explore the prognostic significance of autophagy-related genes (ARGs) in endometrial cancer (EC) using bioinformatics.Methods: The list of ARGs was obtained from the Human Autophagy Database. The differentially expressed ARGs (DEARGs) between the EC and normal endometrial tissue samples were screened from The Cancer Genome Atlas database. Cox regression analysis was performed on the DEARGs to screen the prognostic ARGs and construct risk signatures for overall survival (OS) and progression-free survival (PFS). The hub ARGs were identified from a protein-protein interaction network, and CDKN2A was obtained from the intersection of prognostic ARGs and hub ARGs. The association of CDKN2A expression with clinical characteristics and immune infiltration were analyzed. Finally, the role of CDKN2A in autophagy was confirmed in EC cell lines.Results: CDKN2A, PTK6 and DLC1 were used to establish risk signatures for predicting the survival of EC patients. Receiver operating characteristic curve analysis indicated that the risk signatures can accurately predict both OS and PFS. CDKN2A was the only hub prognostic ARG, and showed significant association with the age, survival status, grade, histological type, body mass index and FIGO (i.e. International Federation of Gynecology and Obstetrics) stage (p < 0.05). Furthermore, CDKN2A expression was also correlated with the infiltration of immune cells, indicating that CDKN2A might play a critical role in regulating the immune microenvironment and immune responses in EC. In addition, silencing of CDKN2A gene promoted autophagy in the HEC-1A cell line and upregulated the expression levels of autophagy-related proteins.Conclusions: CDKN2A is a prognostic factor and therapeutic target in EC, and is likely associated with the tumor immune landscape and autophagy.