A Novel Prognostic Model for DLBCL Patients Based on Cuproptosis-related Genes

Abstract

Abstract Background: The current classification system for diffuse large B-cell lymphoma (DLBCL) cannot fully explain the prognostic differences of DLBCL patients. Cuproptosis is a newly discovered programmed cell death which depends on copper ions. In this study, a prognostic model based on cuproptosis-related genes was constructed using the public database. Methods and materials: COX regression analysis was performed on training set-GSE31312 to construct a prognostic model based on cuproptosis-related genes, and the validation set-GSE181063 was used to verify the prognostic model. GSEA was used to explore the underlying mechanism of the difference in the prognosis of DLBCL patients. Finally, molecular docking was used to screen for compounds that may act on cuproptosis-related genes. Results: A prognostic model based on 5 cuproptosis-related genes was constructed (CDKN2A × 1.547905713 - DLAT × 2.241073725 - DLD × 1.907442964 - LIPT1 × 2.689158994 - MTF1 × 2.069682266) from training set-GSE31312. According to this model, DLBCL patients were divided into high-risk and low-risk groups. The survival time of high-risk patients was significantly shorter than that of the low-risk group (p = 2.636 × 10-7). In the validation set GSE181063, the survival time of the high-risk group was also shorter than low-risk group (p=2.462×10-03). Among the 5 cuproptosis-related genes, only CDKN2A played a tumorigenesis effect. Finally, three small molecule compounds with the lowest binding energy of CDKN2A were found by virtual docking: Irinotecan, Lumacaftor and Nilotinib, which may be used as potential targeted drugs. Conclusion: A prognostic model based on 5 cuproptosis-related genes was constructed, and 3 potential targeted inhibitors of CDKN2A were screened out by molecular docking.