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High Expression of FOXO3 in Gastric Cancer Tissues is Associated with Poor Prognosis and Immune Cell Infiltration by Bingzheng Zhong, Ziwei Yin, Xiaofeng Guo, Xiao Zhang, Xi Dou, Qiang Wang

Background: The purpose of this study was to explore the role of FOXO3 in gastric cancer (GC).
Methods: Data on gastric cancer and normal tissues were collected from the TCGA and GTEx databases. Survival analysis was performed with the Kaplan–Meier method, and the ENCORI online analysis tool was used to predict potential interaction miRNA. The MCPCOUNTER and Tumor Immune Dysfunction and Exclusion (TIDE) algorithm were used to predict the relationship between immune infiltration and FOXO3. Finally, gene set enrichment analysis (GSEA) was used to explore the potential pathways of FOXO3 during the development of GC.
Results: We found that mRNA expression level of FOXO3 was remarkably higher in tumor tissue than in normal tissue, and poor prognoses of GC patients were correlated with higher expression of FOXO3. We also found that hsa-miR-18a-5p and hsa-miR-18b-5p can interact with FOXO3 and that high expression of hsa-miR-18a-5p and hsa-miR-18b-5p predicted better prognoses in GC patients. TP53 mutation was significantly associated with high FOXO3 expression, while ARID1A mutation was associated with low FOXO3 expression. Multiple immune cells were found to be related to the expression of FOXO3, and lower expression of FOXO3 may be better suited to immune checkpoint blockade treatment.
Conclusions: We find that FOXO3 is a potential oncogene and that the transcript level of FOXO3 is related to the mutation of TP53 and ARID1A. In addition, FOXO3 may influence immune infiltration and different signal pathways through sponge adsorption of miRNA to impact the prognoses of stomach adenocarcinoma patients.

DOI: 10.7754/Clin.Lab.2023.230219