The Critical Role of PTEN Mutation in Cellular Process and Drug Selection of Endometrial Cancer

Abstract

Background: Phosphatase and tensin homolog (PTEN) is a frequently mutated genes found in endometrial cancer (EC), making it a potential biomarker for individualized treatment opinions. In this study, a method was designed to evaluate the role of the PTEN mutation in the prognosis and drug selection of EC. We identified the potential alterations in pathways and genes related to the mechanism. Methods: cBioPortal database was used to analyze the PTEN mutation status for EC patients. Kaplan-Meier was used to analyze the prognosis of PTEN mutation in EC patients. GDSC dataset was used to identified the drugs that sensitive to cell lines with PTEN mutation. DEGs between PTEN mutation and wide type group were identified using the edgeR package. GO and KEGG analysis were carried out using the DAVID database. GSEA v3.0 were used to dig out the differences in gene mRNA levels of biological function annotation and pathways between PTEN mutation and wide type patients. PPI network of DEGs was performed using STRING and then visualized using Cytoscope software (3.7.2).Results: Our results showed that PTEN mutation was carried in 68% of EC patients. The mRNA expression level of PTEN was lower in patients with PTEN mutation than that with wide type. Prognosis analysis showed that there were favorable overall survival and progression free survival in EC patients with PTEN mutation. Moreover, it is more sensitive to AKT inhibitor (Afuresertib and AZD5363), and Mcl-1 inhibitor (MIM1) on EC cell lines with PTEN mutation than that with wide type. A total of 216 genes were identified as DEGs. GO analysis showed that DEGs significantly enriched in chemical synaptic transmission, extracellular region, etc.. KEGG analysis suggested that DEGs significantly enriched in categories associated with metabolic progression. GSEA analysis identified signaling pathways including fatty acid metabolism, fructose and mannose metabolism, etc.. PPI network analysis identified top 10 genes and top three clusters.Conclusions: Multiple genes and pathways may play an important role in EC patients with PTEN mutation. These results provide a potential target and therapeutic strategies for patients with PTEN mutation.