Programmed-Cell-Death-Related Signature Reveals Immune Microenvironment Characteristics and Predicts Therapeutic...

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• Diffuse Large B cell Lymphoma (DLBCL) is an aggressive, heterogeneous cancer with significant relapse and resistance challenges.
• Programmed cell death (PCD) pathways influence tumorigenesis, the tumor microenvironment (TME), and drug sensitivity in DLBCL.
• Novel therapeutic strategies targeting PCD are needed for DLBCL management.

Purpose of the Study:

• To develop and validate a prognostic signature based on multiple PCD pathways for DLBCL patients.
• To assess the association of this signature with patient survival, immune infiltration, and drug sensitivity.

Main Methods:

• Systematic analysis of 13 PCD pathways and integration of transcriptomic and clinical data from 832 DLBCL patients.
• Construction of a Programmed Cell Death Score (PCDS) using 20 key PCD-related genes.
• Evaluation of PCDS using survival analysis, drug response profiling, and immune infiltration assessment (CIBERSORT, ESTIMATE, ssGSEA).

Main Results:

• The PCDS robustly stratified DLBCL patients by survival, outperforming conventional clinical indicators.
• High-PCDS tumors showed immune suppression, reduced CD8+ T cell infiltration, and increased PD-1/PD-L1 expression.
• PCDS predicted differential drug sensitivity, suggesting sorafenib/fulvestrant for high-PCDS and NU7441 for low-PCDS patients.

Conclusions:

• A novel PCDS effectively stratifies DLBCL patients by risk and therapeutic responsiveness.
• The PCDS is significantly associated with the TME's immunological characteristics.
• Findings support personalized treatment strategies and clinical decision-making for DLBCL.