Screening of prognostic genes associated with ferroptosis in esophageal adenocarcinoma and the establishment of its prognostic model

We analyzed three gene microarray datasets by GEO2R and obtained differential genes associated with ferroptosis in esophageal adenocarcinoma by obtaining the FerrDb database to obtain ferroptosis-related genes for the intersection.To further elaborate on the functions of differentially expressed genes(DGEs),this study performed gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis on DEGs.We used the Kaplan-Meier plotter database to verify the effect of DGEs genes on the overall survival of esophageal adenocarcinoma.We performed univariate/multifactorial COX regression analysis of DGEs genes associated with esophageal adenocarcinoma prognosis by R language to obtain ferroptosis-associated independent prognostic genes.To further understand the relationship between the upstream molecules of independent prognostic genes and ferroptosis,we obtained the upstream regulatory molecules miRNAs and LncRNAs of prognosis-related ferroptosis genes with the help of the miRWalk database,Oncomi database and StarBase database.we obtained a total of 75 DEGs.These DGEs were mainly enriched in the cellular response to lipids,and negative regulation of intracellular.These DGEs were mainly enriched in the negative regulation of intracellular signaling,positive regulation of cell death,cellular autophagy,HIF-1 signaling pathway,microRNAs in cancer,and ferroptosis.We performed prognostic analysis and univariate/multifactorial COX regression analysis on 75 ferroptosis-related genes and established four independent genes for esophageal adenocarcinoma,ATF3,ATM,ATG5,and HMGB1.The study also established hsa-miR-876-5p,hsa-miR-186-5p,hsa-miR-421,hsa-miR-505-3p,hsa-miR-503-5p,hsa-miR-299-3p and hsa-miR-191-5p,seven miRNAs with upstream regulation of LncRNAs.these miRNAs can be competitively bound by LncRNAs to prevent the inhibition of translation of target gene expression by miRNAs.In conclusion,our study identified four esophageal adenocarcinoma independent prognostic genes and their upstream regulatory molecules.These genes are involved in the ferroptosis regulation of cells and also play an important role in tumor therapy and drug resistance as one of the disease therapeutic targets.The study suggests that by targeting ATF3,ATM,ATG5,HMGB1 and their upstream regulatory molecules is a new direction for the treatment of esophageal adenocarcinoma.