High ATF4 Expression Is Associated With Poor Prognosis, Amino Acid Metabolism, and Autophagy in Gastric Cancer

BackgroundThe role of activating transcription factor 4 (ATF4) underlying gastric cancer (GC) remains unclear. The purpose of this study was to investigate the expression levels and biological functions of ATF4 in GC.MethodsExpression of ATF4 was detected by quantitative PCR (qPCR), Western blotting, and immunohistochemistry. Cox regression was used for survival analysis and the construction of the nomogram. Immunofluorescence was used to identify the intracellular localization of ATF4. Knockdown and overexpression of ATF4 in GC cells followed by wound healing and Transwell assays, EdU and Calcein-AM/propidium iodide (PI) staining, and cell cycle detection were performed to examine its function in vitro. Transmission electron microscopy was performed to assess the autophagy levels upon ATF4 silencing. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and gene set enrichment analysis (GSEA) were used to determine gene enrichment. SPSS 22.0 software, GraphPad Prism 7.0, and R version 3.6.1 were used for statistical analysis.ResultsATF4 expression was upregulated in GC cells and tissues compared with corresponding normal tissues. Survival analysis suggested that a high ATF4 expression was strongly associated with worse overall survival (OS) of GC patients (p