A novel necroptosis-related miRNA signature for predicting the prognosis of esophageal cancer and immune infiltration analysis

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Background: The prognostic value of necroptosis-related microRNAs (miRNAs), which are important in tumorigenesis and development, remains unclear. Therefore, we aimed to screen prognostic necroptosis-related miRNAs in esophageal cancer (EC). Methods: Nine necroptosis-related miRNA expression profiles and associated clinical data of EC patients were obtained from The Cancer Genome Atlas (TCGA) database. The relationships between necroptosis-related miRNAs and overall survival (OS) were determined via Cox regression model analysis. Target genes of the miRNAs were investigated in TargetScan, miRDB, and miRTarBase. The biological functions of these genes were evaluated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. For the most significant correlation between miR-425-5p expression and the survival of EC patients, the effect of miR-425-5p on necroptosis was explored in EC cells. The relationship between targeted gene expression and immune infiltration was also analyzed and validated. Results: Hsa-miR-425-5p, hsa-miR-500a-3p, hsa-miR-7-5p and hsa-miR-200a-5p were selected for the construction of a prognostic signature based on their correlation with the survival of EC patients. EC patients were divided into high- and low-risk groups according to the median value of the risk score. Patients in the high-risk group tended to have higher death rates than those in the low-risk group (P<0.05). The risk score was an independent prognostic indicator for the OS of EC patients [hazard ratio (HR) >1, P<0.05]. The prognostic model had good predictive efficiency. The genes targeted by necroptosis-related miRNAs were significantly enriched in apoptosis etc. The inhibition of miR-425-5p promoted necroptosis in EC cells by targeting branched chain amino acid transaminase 1 (BCAT1). The expression level of BCAT1 was significantly correlated with immune infiltration. Conclusions: A necroptosis-related four-miRNA model was constructed successfully to predict the potential value of the four miRNAs in the prognosis of EC, which can be conducive to promoting the therapeutic effect on EC.

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