Identification of B-cell lymphoma subsets by plasma protein profiling using recombinant antibody microarrays

Abstract

B-cell lymphoma (BCL) heterogeneity represents a key issue, often making the classification and clinical management of these patients challenging. In this pilot study, we outlined the first resolved view of BCL disease heterogeneity on the protein level by deciphering disease-associated plasma biomarkers, specific for chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma, using recombinant antibody microarrays targeting mainly immunoregulatory proteins. The results showed the BCLs to be heterogeneous, and revealed potential novel subgroups of each BCL. In the case of diffuse large B-cell lymphoma, we also indicated a link between the novel subgroups and survival.

Plasma immunoprofiling of patients with high-risk diffuse large B-cell lymphoma: a Nordic Lymphoma Group study

“…( A ) Subdivision of DLBCL patients into subgroups DLBCLa and DLBCLb based on a 23 biomarker signature identified in our previous study. 1 ( B ) Kaplan–Meier plot demonstrating OS of DLBCLa and DLBCLb, log-rank P =0.07 for OS. ( C ) Kaplan–Meier plot demonstrating FFS of DLBCLa and DLBCLb, log-rank P =0.05 for FFS.…”

“…On the basis of plasma samples taken at diagnosis, and the protein signature of 23 plasma proteins with prognostic impact found in a previous pilot study from our group, 1 patients in the present study could be divided into two distinct subgroups, denoted DLBCLa and DLBCLb, by unsupervised hierarchical clustering. The proteins in the profile included immunoregulatory proteins such as T-helper cytokines, chemotactic proteins and complement factors.…”

“…In a recent pilot study we showed that plasma immunoprofiling, using recombinant antibody microarrays, could be used to decipher DLBCL heterogeneity on the protein level, indicating potential novel patient subgroups that might be linked to survival. 1 Here, we have expanded these immunoprofiling efforts by examining the immunoprofiles of DLBCL patients, using longitudinal plasma samples collected at the time of diagnosis and during the treatment. Our aim was to search for prognostic and potentially predictive protein profiles in plasma samples from DLBCL patients.…”

“…4, 5 In addition, a recent pilot study using plasma samples from DLBCL patients revealed a protein immunoprofile of 23 plasma proteins that could be used to differentiate the patients into two subgroups with significantly different overall survival (OS). 1 Here, our approach was to expand the immunoprofiling of DLBCL patients, but in addition also target plasma proteins that are connected to proliferation and survival of the tumor cells.…”

Molecular biosensors: promising new tools for early detection of cancer

“…The protein arrays lead to detection of possible novel biomarkers and enable a deeper understanding of the printed proteins related to signaling pathways on the slides. 43,44 There are several stages between the discovery of biomarkers and their clinical use in patients with cancer. 45 Post-genomic technologies and bioinformatics tools help to identify novel candidate markers with the integration of relevant information, such as gene expression, mutations, single nucleotide polymorphisms, and cancer biology.…”