Comprehensive analysis and experiment validation of five cuproptosis-related genes in prognosis, immune infiltration and metabolic characterization of pancreatic cancer.
<h4>Background</h4>Cuproposis is a new-found mechanism of cell death, and the role of cuproposis-related genes (CRGs) in pancreatic cancer prognosis remains uncertain.<h4>Methods</h4>DECRGs were identified from TCGA and GTEx databases. Five OS-associated hub genes were screen...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0323458 |
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| Summary: | <h4>Background</h4>Cuproposis is a new-found mechanism of cell death, and the role of cuproposis-related genes (CRGs) in pancreatic cancer prognosis remains uncertain.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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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| ISSN: | 1932-6203 |