Comprehensive analysis and experiment validation of five cuproptosis-related genes in prognosis, immune infiltration and metabolic characterization of pancreatic cancer

对胰腺癌预后、免疫浸润和代谢特征中五个铜凋亡相关基因进行综合分析和实验验证

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Abstract

BACKGROUND: Cuproposis is a new-found mechanism of cell death, and the role of cuproposis-related genes (CRGs) in pancreatic cancer prognosis remains uncertain. METHODS: DECRGs were identified from TCGA and GTEx databases. Five OS-associated hub genes were screened using Cox regression and LASSO analyses. A prognostic model was constructed and validated by survival analysis. GSEA, gene mutation, small-molecule drugs, immune-infiltrating and TF/miRNA/mRNA network were investigated to determine the underlying mechanism of 5-CRGs. In addition, RT-qPCR, and WB were applied to validate the expression of 5-CRGs. CCK8, colony formation and transwell assays were used to prove the function of LIPT1 in PC. RESULTS: PDP1, DLAT, DBT, LIAS, and LIPT1 were screened as hub genes. 5-CRGs prognostic model established the low-risk population has a longer OS. There was a high the risk score value for the prediction in clinicopathological features. The forest plots showed that age, N stage and the RiskScore were the significant independent risk indicators. T cells CD4 memory resting and Mast cells are the amplest immune cell subpopulations in the high-score individuals. The expression of 5 CRGs exhibited significant differences in PC cell lines and tissues, LIPT1-knockdowning inhibited proliferation and invasion of pancreatic cancer cell lines. CONCLUSION: Five CRGs relevant to pancreatic cancer prognosis were identified. Meanwhile, a new and accurate five CRGs prognostic model of pancreatic cancer was constructed. In addition, LIPT1 may promote proliferation, invasion and migration of pancreatic cancer cell lines. This may have a specific guiding value for future development of precise anti-cancer treatment strategies.

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