Search

Background: Epithelial ovarian cancer (EOC) is the deadliest malignancy among the gynecologic tumors, and ovarian serous cystadenocarcinoma (OV) is the dominant histological type. Ferroptosis is a novel iron-dependent, programmed form of cell death, and agents that trigger ferroptosis may constitute potential anti-cancer therapies. Materials and Methods: We herein extracted the genes that participate in the process of ferroptosis from the online FerrDb database to create a ferroptosis-related genome (FRG), and then comprehensively analyzed the relationship between the mRNA expression of each gene and the clinicopathologic features of The Cancer Genome Atlas (TCGA)-OV cohort. Results: We found that most of the FRG genes were differently expressed between OV and normal ovarian tissue and were significantly related to the prognosis of OV. In addition, gene ontology (GO) analysis revealed that the candidate genes of the FRG were primarily associated with responses to nutrient levels, oxidative stress, oxygen levels, and neuronal death. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that candidate genes of the FRG were primarily associated with ferroptosis, hepatitis B, mitophagy, prostate cancer, and bladder cancer. The protein-protein interaction (PPI) network exhibited 132 nodes, 565 edges, an average node degree of 9.94, and an average local clustering coefficient of 0.539, indicating that the proteins were closely interrelated with one another and constitute a biological cluster. A comprehensive analysis of the top 5 genes involved in promoting and preventing ferroptosis revealed that these genes were differently expressed between OV and normal ovarian tissue, were significantly related to the prognosis of OV, reflected excellent diagnostic value, and were significantly correlated with immune cell infiltration in the tumor microenvironment (TME), polarization of macrophages, and with immune checkpoints. The protein levels of top 5 genes involved in promoting ferroptosis were differentially expressed between OV and normal ovarian tissue, and the top 5 genes involved in preventing ferroptosis were constitutively expressed in most of the normal tissues and tumors. Conclusions: We herein ascertained that the majority of the FRG was differentially expressed between OV and normal ovarian tissue, that the genes were significantly related to prognosis, and that the dysregulation of ferroptosis appeared to influence the development and progression of OV. The FRG showed an excellent diagnostic value for OV, and we postulate that it is significantly correlated with immune cell infiltration and immune checkpoints in the TME. We posit that targeting ferroptosis might comprise a novel anti-cancer therapy in OV. [ABSTRACT FROM AUTHOR]

Background: Ferroptosis is a recently recognized non-apoptotic cell death that is distinct from the apoptosis, necroptosis and pyroptosis. Considerable studies have demonstrated ferroptosis is involved in the biological process of various cancers. However, the role of ferroptosis in esophageal adenocarcinoma (EAC) remains unclear. This study aims to explore the ferroptosis-related genes (FRG) expression profiles and their prognostic values in EAC. Methods: The FRG data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate cox regressions were used to identify the prognostic FRG, and the predictive ROC model was established using the independent risk factors. GO and KEGG enrichment analyses were performed to investigate the bioinformatics functions of significantly different genes (SDG) of ferroptosis. Additionally, the correlations of ferroptosis and immune cells were assessed through the single-sample gene set enrichment analysis (ssGSEA) and TIMER database. Finally, SDG were verified in clinical EAC specimens and normal esophageal mucosal tissues. Results: Twenty-eight significantly different FRG were screened from 78 EAC and 9 normal tissues. Enrichment analyses showed these SDG were mainly related to the iron-related pathways and metabolisms of ferroptosis. Gene network demonstrated the TP53, G6PD, NFE2L2 and PTGS2 were the hub genes in the biology of ferroptosis. Cox regression analyses demonstrated four FRG (CARS1, GCLM, GLS2 and EMC2) had prognostic values for overall survival (OS) (all P < 0.05). ROC curve showed better predictive ability using the risk score (AUC = 0.744). Immune cell enrichment analysis demonstrated that the types of immune cells and their expression levels in the high-risk group were significant different with those in the low-risk group (all P < 0.05). The experimental results confirmed the ALOX5, NOX1 were upregulated and the MT1G was downregulated in the EAC tissues compared with the normal esophageal mucosal tissues (all P < 0.05). Conclusions: We identified differently expressed ferroptosis-related genes that may involve in EAC. These genes have significant values in predicting the patients' OS and targeting ferroptosis may be an alternative for therapy. Further studies are necessary to verify these results of our study. [ABSTRACT FROM AUTHOR]