International Prognostic Index-Based Immune Prognostic Model for Diffuse Large B-Cell Lymphoma

Abstract

BackgroundThe International Prognostic Index (IPI) is widely used to discriminate the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). However, there is a significant need to identify novel valuable biomarkers in the context of targeted therapy, such as immune checkpoint blockade (ICB).MethodsGene expression data and clinical DLBCL information were obtained from The Cancer Genome Atlas and Gene Expression Omnibus datasets. A total of 371 immune-related genes in DLBCL patients associated with different IPI risk groups were identified by weighted gene co-expression network analysis, and eight genes were selected to construct an IPI-based immune prognostic model (IPI-IPM). Subsequently, we analyzed the somatic mutation and transcription profiles of the IPI-IPM subgroups as well as the potential clinical response to immune checkpoint blockade (ICB) in IPI-IPM subgroups.ResultsThe IPI-IPM was constructed based on the expression of CMBL, TLCD3B, SYNDIG1, ESM1, EPHA3, HUNK, PTX3, and IL12A, where high-risk patients had worse overall survival than low-risk patients, consistent with the results in the independent validation cohorts. The comprehensive results showed that high IPI-IPM risk scores were correlated with immune-related signaling pathways, high KMT2D and CD79B mutation rates, and upregulation of inhibitory immune checkpoints, including PD-L1, BTLA, and SIGLEC7, indicating a greater potential response to ICB therapy.ConclusionThe IPI-IPM has independent prognostic significance for DLBCL patients, which provides an immunological perspective to elucidate the mechanisms of tumor progression and sheds light on the development of immunotherapy for DLBCL.

Analysis of the regulatory mechanisms of prognostic immune factors in thyroid cancer

“…); abundance is positively correlated ( 31 ). SYNDIG1 is a prognostic immune factor in diffuse large B-cell lymphoma and breast cancer ( 32 , 33 ). DACT1 belongs to the DACT (Disheveled-associated antagonist of β-catenin) family and is a methylation biomarker for DACT1 in esophageal squamous cell carcinoma ( 34 ).…”

The genetic polymorphisms of immune‐related genes contribute to the susceptibility and survival of lymphoma

“…IL‐12 plays a central role in the cellular and humoral pathways, which is mainly produced by antigen‐presenting cells and acts on T cells and natural killer (NK) by inducing IFN‐γ production 72,73 . Recently, the IPI‐based immune prognostic model based on eight genes including IL12A had independent prognostic significance in DLBCL patients, which provided an immunological perspective for elucidating the tumor progression mechanism of DLBCL, and were also useful for DLBCL immunotherapy 74 . We found that the GC genotype had the lowest OS, and the GG and CC genotypes had similar OS levels in lymphoma patients.…”

Aggressive diffuse large B‐cell lymphoma manifested by splenic rupture progressed 2 months after transverse myelitis: an autopsy case report

“… 8 We do not know potential unknown genetic causes because we have not performed whole‐genome sequences for germline and somatic genetic variants, which is beyond the scope of this case report. 9 …”