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.

Bioinformatics-based analysis of the relationship between core genes and immune infiltration and tumor metastasis in esophageal cancer

We analysed four gene microarray datasets by GEO2R and obtained differential genes expressed in oesophageal cancer.To further elaborate the functions of DGEs,this study performed gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of DEGs.We constructed protein interaction networks of DGEs through the String database and screened core genes.We used the GEPIA online database with the Kaplan-Meier plotter database to verify the expression of Hub genes in expressed normal versus tumour tissues and the effect of Hub genes on overall and disease-free survival in oesophageal cancer.To further understand the relationship between Hub gene and tumour metastasis,we analysed the difference in Hub gene expression in patients without metastatic oesophageal cancer versus those with metastatic oesophageal cancer with the help of the HCMDB database.The relationship between Hub genes and tumour immune infiltration was analysed by the TIMER database.We obtained a total of 149 DEGs,of which 49 were up-regulated genes and 100 were down-regulated genes.These DGEs were importantly enriched in IL-17 signalling pathway,ECM-receptor interactions,p53 signalling pathway,estrogen signalling pathway,complement and coagulation cascade response.We screened 10 Hub genes,MMP9,CXCL8,COL1A1,TIMP1,POSTN,MMP3,MMP1,COL3A1,SERPINE1,LUM,among 149 DGEs.hub genes were all up-regulated in expression in esophageal cancer tissues,in addition,MMP9,T1MP1,CXCL8,POSTN and The expression of COL3A1,LUM,MMP1,MMP3,MMP9,POSTN,SERPINE1 and TIMP1 was positively correlated with the infiltration of immune cells in the tumor microenvironment.In conclusion,our study identified 10 signature genes for oesophageal cancer.These genes are associated with the development,metastasis,prognosis and immune infiltration of oesophageal cancer and may be markers of development,metastasis and prognosis as well as targets for immunotherapy.