Development and validation of a cuproptosis-associated prognostic model for diffuse large B-cell lymphoma

Area of Science:

• Oncology
• Cell Death Research
• Biomarker Discovery

Background:

• Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous cancer requiring better prognostic markers.
• Cuproptosis, a novel copper-dependent programmed cell death (PCD), is linked to mitochondrial metabolism.
• The prognostic significance of cuproptosis-related genes (CRGs) in DLBCL is not well understood.

Purpose of the Study:

• To investigate the prognostic value of CRGs in DLBCL.
• To explore DLBCL heterogeneity using CRG expression profiles.
• To develop a novel prognostic model for DLBCL patients.

Main Methods:

• Consensus clustering based on CRG expression to identify DLBCL subtypes.
• Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression for prognostic model construction.
• Validation using Cox regression, Kaplan-Meier curves, ROC curves, and external datasets.

Main Results:

• Two distinct DLBCL subtypes with differential survival, biological functions, drug sensitivity, and immune microenvironments were identified.
• A CRG-based prognostic model and nomogram were developed, showing improved accuracy over the International Prognostic Index (IPI).
• The model effectively predicted clinical characteristics, immune cell infiltration, and patient prognosis.

Conclusions:

• CRGs are associated with DLBCL prognosis and can be used to characterize disease heterogeneity.
• A novel CRG-based prognostic signature and nomogram can enhance risk stratification for DLBCL patients.
• This research provides potential new therapeutic targets and prognostic predictors for DLBCL.