Prediction of Prognosis in Patients With Endometrial Carcinoma and Immune Microenvironment Estimation Based on Ferroptosis-Related Genes

Background: Ferroptosis, a form of non-apoptotic cell death, has aroused worldwide interest in cancer researchers. However, the current study about the correlation between ferroptosis-related genes (FRGs) and endometrial cancer (EC) remains limited.

Methods: First, the transcriptome profiling and clinical data of EC patients were downloaded from The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) program as the training group and testing group, respectively. FRGs were acquired through literature mining. Then, we used R 4.1.1 software to screen the differently expressed FRGs from TCGA, which was also connected with the prognosis of EC patients. Subsequently, the risk score of each tumor sample was identified by LASSO regression analysis, and we classified these samples into the high- and low-risk groups in the light of the median risk score. Receiver operating characteristic (ROC) curve analysis and Kaplan-Meier analysis were performed to assess the accuracy of this signature. Significantly, the data from CPTAC was used to validate the prediction model externally. Furthermore, we evaluated the immune microenvironment in this model via single-sample gene set enrichment analysis (ssGSEA).

Results: Among the 150 FRGs, 6 differentially expressed genes (DEGs) based on TCGA had a relationship with the prognosis of EC patients, namely, TP53, AIFM2, ATG7, TLR4, PANX1 and MDM2. The survival curve indicated a higher survival probability in the low-risk group. Moreover, the FRGs-based signature acted well in the prediction of overall survival (OS). The results of external verification confirmed the prediction model we established. Finally, ssGSEA revealed significant differences in the abundance of 16 immune cells infiltration and the activity of 13 immune functions between different risk groups.

Conclusion: We identified a novel ferroptosis-related gene signature which could concisely predict the prognosis and immunotherapy in EC patients.