Integrative analysis of a novel immunogenic PANoptosis‑related gene signature in diffuse large B-cell lymphoma for prognostication and therapeutic decision-making

Abstract

Abstract This study aimed to develop a PANoptosis-related gene prognostic index (PANGPI) to explore its potential value in predicting the prognosis and immunotherapy response of diffuse large B-cell lymphoma (DLBCL). Differentially expressed genes of DLBCL from GEO databases were analyzed and mapped to the PANoptosis gene set. The independent prognostic value of the PANGPI signature was evaluated using LASSO Cox regression and multivariate Cox regression. Additionally, the tumor infiltrating lymphocyte (TIL) characteristics and mutation landscape of both subgroups were evaluated, and drug sensitivity was predicted using the GDSC database. Furthermore, in silico docking and molecular dynamic simulation studies were presented to elucidate the mode of interaction of these predicted drugs. The PANGPI risk score was an independent risk factor for the prognosis of patients with DLBCL and exhibited good prognostic predictive performance. Furthermore, the cytolytic activity of the TILs was positively correlated with the PANGPI scores. Additionally, the PANGPI enabled the identification of 3 chemotherapeutic agents, including BMS-536924, Gefitinib, Navitoclax for DLBCL patients in the high-risk group. We established a novel PANoptosis-related gene subtyping system in DLBCL, which could shed a novel light on the development of new biomarkers for DLBCL.

Keywords

• Diffuse large B-cell lymphoma
• PANoptosis
• Prognostic index
• Tumor infiltrating lymphocyte
• Drug sensitivity