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Investigation and validation of cuproptosis-related ferroptosis genes in gastric cancer: Exploring the Role of MYB in the Process

bioinformatics
cell-biology
molecular-biology
gastroenterology-and-hepatology
oncology

Abstract

Backgrounds: Gastric cancer (GC) is a common malignant tumor of the digestive tract. Ferroptosis and cuproptosis lead to a new way of tumor cell death. The aim of this article is to search for new prognostic biomarkers for GC by combining two modes of death and to validate them experimentally.
Methods: Downloading information from the TCGA and GEO databases about patients with GC. Cuproptosis-related ferroptosis genes (CRFGs) were obtained by correlation analysis. Identify differential CRFGs and perform enrichment analysis. Prognosis-related CRFGs were detected by univariate Cox analysis. LASSO regression to build prognostic models, where the TCGA dataset is used as the train set and the GEO dataset is used as the test set. The model was validated and analyzed for TME, GSVA, immune cell infiltration, TMB, and drug sensitization. We eventually selected one of the prognosis-related CRFGs for qRT-PCR, Western blot, transwell and wound-healing assay.
Results: We obtained 155 CRFGs by correlation analysis and screened 103 from the analysis of difference. Univariate Cox analysis screened for 9 prognosis-related CRFGs. We modeled by LASSO regression and identified 7 model prognostic CRFGs (DUSP1, HIF1A, MYB, NOX4, PRKAA2, SLC2A3, and TGFBR1). The test group validates the train group well. MYB is the only gene whose expression is the opposite of the risk score, so we chose this gene for subsequent analysis. The expression of MYB in the cell lines and tissues was consistent with our bioinformatic results, but the expression levels of MYB gene are positively correlated with GC cellular growth levels, the same is true for migration and invasive capacity. Single-cell sequencing results indicate that MYB is expressed in immune cells, which may influence GC development. All meaningful delineations as p<0.05.
Conclusion: We established a novel model predicting gastric cancer prognosis based on CRFGs, identifying seven CRFGs associated with prognosis. Among these, high MYB expression promotes the development of GC cells, but its expression in immune cells may exert an inhibitory effect on gastric cancer.
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