Meta-Analysis of MS-Based Proteomics Studies Indicates Interferon Regulatory Factor 4 and Nucleobindin1 as Potential Prognostic and Drug Resistance Biomarkers in Diffuse Large B Cell Lymphoma

SIMPLE SUMMARY: Mass spectrometry-based proteomics studies have suggested various proteins as diagnostic, prognostic, and druggable targets in diffuse large B cell lymphoma. Given rather divergent results in previous mass-spectrometry-based studies, we aimed to review these studies to obtain a consensus list of proteins. From these, we extracted the most consistently significantly regulated proteins. Interferon regulatory factor4, annexinA5, and nucleobindin1 were identified as the most consistently reported proteins. Interferon regulatory factor 4 was identified as a target in immunohistochemistry, proteomics, and genomics research studies. AnnexinA5 and nucleobindin1 appeared as the top up-regulated proteins that may be involved in drug resistance. Additionally, nucleobindin1 and interferon regulatory factor 4 showed a correlation with inferior prognosis based on transcriptomics data. The results of functional enrichment analysis showed that proteins observed as dysregulated in reviewed studies displayed functions occurring in the light zone of the germinal center (e.g., immune synapse formation, and cell migration). ABSTRACT: The prognosis of diffuse large B cell lymphoma (DLBCL) is inaccurately predicted using clinical features and immunohistochemistry (IHC) algorithms. Nomination of a panel of molecules as the target for therapy and predicting prognosis in DLBCL is challenging because of the divergences in the results of molecular studies. Mass spectrometry (MS)-based proteomics in the clinic represents an analytical tool with the potential to improve DLBCL diagnosis and prognosis. Previous proteomics studies using MS-based proteomics identified a wide range of proteins. To achieve a consensus, we reviewed MS-based proteomics studies and extracted the most consistently significantly dysregulated proteins. These proteins were then further explored by analyzing data from other omics fields. Among all significantly regulated proteins, interferon regulatory factor 4 (IRF4) was identified as a potential target by proteomics, genomics, and IHC. Moreover, annexinA5 (ANXA5) and nucleobindin1 (NUCB1) were two of the most up-regulated proteins identified in MS studies. Functional enrichment analysis identified the light zone reactions of the germinal center (LZ-GC) together with cytoskeleton locomotion functions as enriched based on consistent, significantly dysregulated proteins. In this study, we suggest IRF4 and NUCB1 proteins as potential biomarkers that deserve further investigation in the field of DLBCL sub-classification and prognosis.