Abstract
Introduction: Endometrial cancer is one of the most common uterine cancers worldwide. AKT is reported to regulate progesterone receptor B dependent transcription and angiogenesis in endometrial cancer. However, the potential mechanisms of AKT in the tumor progression of endometrial cancer remain unclear.Methods: We used GSE72708 with gene expression profiles of AKT regulation from the GEO database. We performed GSEA analysis to explore pathway enrichments. We found that most upregulated enriched pathways in siAKT group were associated with acid metabolism and immune network. Endometrial cancer and various signaling pathways were downregulated enriched. Moreover, different molecular mechanism of regulation between progestin (R5020) and AKT was identified, which were related to VEGF signaling pathway. The hub genes were evaluated by immunohistochemical staining of endometrial cancer tissues.Results: We screened out a total of 623 differentially expressed genes among different groups. According to weighted gene co-expression network analysis (WGCNA) method, four distinct modules were identified. We found brown module showed a very high positive correlation with siAKT group and a very high negative correlation with R5020 group. A total of six hub genes including PBK, BIRC5, AURKA, GTSE1, KNSTRN, and PSMB10 were finally identified associated with AKT1. In addition, the data also shows that the higher expression of AKT1, GTSE1, BIRC5, AURKA, and KNSTRN is significantly associate with poor prognosis of endometrial cancer.Conclusion: Our study identified six hub genes related to the prognosis of endometrial cancer, which may provide new insights into the underlying biological mechanisms driving the tumorigenesis of endometrial cancer, especially in AKT1 regulation.
Highlights
Endometrial cancer is one of the most common uterine cancers worldwide
We performed a multi-steps analysis to explore the molecular mechanisms of AKT1 in the pathogenesis of endometrial cancer
Results suggested that different molecular mechanism of regulation between R5020 and AKT, which were related to VEGF signaling pathway
Summary
Endometrial cancer is one of the most common uterine cancers worldwide. AKT is reported to regulate progesterone receptor B dependent transcription and angiogenesis in endometrial cancer. The potential mechanisms of AKT in the tumor progression of endometrial cancer remain unclear. Endometrial cancer (EC) is the most common uterine cancer that is commonly diagnosed worldwide, accounting for ∼382,069 new cases every year with an incidence rates of 8.4 per population [1]. The identification of biological ways to improve the prognosis or explore significant molecular functions in endometrial cancer is necessary. This could help understand its pathogenesis and provide more effective treatment of endometrial cancer
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