P1191: A NOVEL PROGNOSTIC MODEL OF DLBCL PATIENTS BASED ON CUPROPTOSIS RELATED GENES

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Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical 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 depend on copper ions. However, the potential role of cuproptosis in the prognosis of DLBCL patients remains unclear. Aims: In this study, a prognostic model based on cuproptosis-related genes was constructed using public database. The target compounds that may act on copper death related genes were also searched. Methods: COX regression analysis was performed on training set-GSE31312 to construct a prognostic model based on copper death-related genes, and validation set-GSE181063 was used to verify the prognostic model. GSEA was used to explore the underlying mechanism of the difference in prognosis of DLBCL patients. Finally, molecular docking was used to screen for compounds that may act on cuproptosis-related genes. Results: Uni-COX regression analysis was performed on cuproptosis-related genes of GSE31312, and 6 key cuproptosis-related genes that significantly affected the prognosis of patients were screened out. Multi-COX regression analysis was performed on these 6 cuproptosis-related genes. 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). 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 = 2.251 × 10-4). Among the 5 cuproptosis-related genes, only CDKN2A played a tumorigenesis effect. Finally, three small molecules 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. Keywords: DLBCL, Prognostic factor

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