Proteomic approaches to the study of malignant lymphoma: Analyses on patient samples

Abstract

We describe the application of proteomic techniques for protein profiling and biomarker discovery in malignant lymphoma. Hematologic malignancies are primarily characterized by their clinical, morphological, immunophenotypical, and molecular-genetic features. However, when based on these parameters, apparently identical lymphomas may show distinct clinical courses, suggesting underlying biological heterogeneity. Recent proteomic analyses have identified differences in protein expression both with regard to subclassification of the malignant lymphoma entities, as well as in correlation with clinical outcome. In this review, studies on quantification of differential protein expression in and between malignant lymphoma entities are included. Studies are included that are based on patient samples, that is, serum/plasma or cytological specimens, as well as intact tumor tissues, together with studies that focus on tumor cells alone, or in conjunction with the tumor microenvironment. For biomarker discovery in malignant lymphoma, these approaches are used to uncover the underlying biological mechanisms and identify proteins with potential diagnostic and prognostic utility, either as predictive biomarkers or as novel future treatment targets.

Plasma proteomic analysis reveals altered protein abundances in HIV‐infected patients with or without non‐Hodgkin lymphoma

“…Over the past decade, researchers using proteomic approaches have provided information on quantitative and qualitative protein patterns in the blood to identify potential cancer biomarkers. 8,9 However, only a minority of published lymphoma proteomic studies have investigated protein expression in patient blood samples, [10][11][12][13][14][15] particularly samples from patients with AIDS-NHL. Xu et al 16 used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to build four models of serum protein fingerprints for identifying potential biomarkers of diffuse large B-cell lymphoma (DLBCL) and distinguishing prognostic markers.…”

Proteomics identifies apoptotic markers as predictors of histological transformation in patients with follicular lymphoma

“…We analyzed FL tumor cells in their tissue surroundings, allowing for a better understanding of the biological background behind the neoplastic process. 15 Various immune system processes were affected with changes involving B-cell receptor, NF-κB, and PI3K signaling, suggesting variations not only in the B-cell derived lymphoma cells but also differences in the nonneoplastic TME. Especially noteworthy, PAX5, a key B-cell transcription factor, was upregulated in st-FL samples.…”

“… 24 With the rapid evolution of modern targeted treatment and personalized medicine, novel therapeutic strategies may not only be aimed directly at tumor cells but also at the components of TME. 15 , 53 , 54 Thus, an improved understanding of the interplay between neoplastic and nonneoplastic factors may aid the discovery of novel predictive markers of HT. With the presented omics data, we have conducted a comprehensive study of proteins that underlie biological differences among individual FL tumors.…”

“… 12 Moreover, analysis of the proteome has the potential to capture novel aspects of tumor heterogeneity, contributing to biomarker discovery and providing candidates for novel targeted therapies in modern precision medicine. 13 , 14 Given that the proteome is adaptive and changes in response to various factors acting at different biological levels, 15 , 16 , 17 a better understanding of the proteome in FL could provide key insights into the biological mechanisms that drive transformation in FL. 14 , 18 …”

S100A9 and ORM1 serve as predictors of therapeutic response and prognostic factors in advanced extranodal NK/T cell lymphoma patients treated with pegaspargase/gemcitabine

“…Proteomic technology has emerged as a valuable tool to screen alterations in protein profilings of serum 8 . In cancer development, crucial proteins from cancer cells and tumor microenvironment are secreted into serum.…”