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Abstract
Cuproptosis-related genes (CRGs) are important for tumor development. However, the functions of CRGs across cancers remain obscure. We performed a pan-cancer investigation to reveal the roles of CRGs across cancers. In an analysis of 26 cancers, 12 CRGs were differentially expressed, and those CRGs were found to have prognostic value across different cancer types. The expression of CRGs exhibited varied among tumors of 6 immune subtypes and were significantly correlated with the 16 sensitivities of drugs. The expression of CRGs were highly correlated with immunological subtype and tumor microenvironment (TME) of prostate cancer. We also established CRGs-related prognostic signatures that closely correlated with prognosis and drug sensitivity of prostate cancer patients. Single-cell RNA-seq revealed that several CRGs were enriched in the cancer cells. Finally, an in vitro experiment showed that elesclomol, a cuproptosis inducer, targets ferredoxin 1 and suppress cell viability in prostate cancer cells. In conclusion, we carried out a comprehensive investigation for determining CRGs in differential expression, prognosis, immunological subtype, TME, and cancer treatment sensitivity across 26 malignancies; and validated the results in prostate cancer. Our research improves pan-cancer knowledge of CRGs and identifies more effective immunotherapy strategies.
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1 Medical School of Nantong University, Nantong, China (GRID:grid.260483.b) (ISNI:0000 0000 9530 8833); Jiangnan University Medical Center, Department of Urology, Wuxi, China (GRID:grid.258151.a) (ISNI:0000 0001 0708 1323); Nantong University, Department of Urology, Wuxi No. 2 Hospital, Wuxi, China (GRID:grid.260483.b) (ISNI:0000 0000 9530 8833); Nanjing Medical University, Department of Urology, Wuxi No. 2 Hospital, Wuxi, China (GRID:grid.89957.3a) (ISNI:0000 0000 9255 8984)
2 Jiangnan University Medical Center, Department of Urology, Wuxi, China (GRID:grid.258151.a) (ISNI:0000 0001 0708 1323); Jiangnan University, Wuxi School of Medicine, Wuxi, China (GRID:grid.258151.a) (ISNI:0000 0001 0708 1323); Nantong University, Department of Urology, Wuxi No. 2 Hospital, Wuxi, China (GRID:grid.260483.b) (ISNI:0000 0000 9530 8833); Nanjing Medical University, Department of Urology, Wuxi No. 2 Hospital, Wuxi, China (GRID:grid.89957.3a) (ISNI:0000 0000 9255 8984)
3 Medical School of Nantong University, Nantong, China (GRID:grid.260483.b) (ISNI:0000 0000 9530 8833); Jiangnan University Medical Center, Department of Urology, Wuxi, China (GRID:grid.258151.a) (ISNI:0000 0001 0708 1323); Jiangnan University, Wuxi School of Medicine, Wuxi, China (GRID:grid.258151.a) (ISNI:0000 0001 0708 1323); Nantong University, Department of Urology, Wuxi No. 2 Hospital, Wuxi, China (GRID:grid.260483.b) (ISNI:0000 0000 9530 8833); Nanjing Medical University, Department of Urology, Wuxi No. 2 Hospital, Wuxi, China (GRID:grid.89957.3a) (ISNI:0000 0000 9255 8984)