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.
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http://dx.doi.org/10.1002/jgm.3648 | DOI Listing |
Acta Neurochir (Wien)
January 2025
Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany.
In recent years, it has been increasingly recognized that tumor growth relies not only on support from the surrounding microenvironment but also on the tumors capacity to adapt to - and actively manipulate - its niche. While targeting angiogenesis and modulating the local immune environment have been explored as therapeutic approaches, these strategies have yet to yield effective treatments for brain tumors and remain under refinement. More recently, the nervous system itself has been explored as a critical environmental support for cancer, with extensive neuro-tumoral interactions observed both intracranially and in extracranial sites containing neural components.
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View Article and Find Full Text PDFAlzheimers Dement
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Weill Cornell Medicine, New York, NY, USA.
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