Quantitative proteomic analysis of cerebrospinal fluid from patients with diffuse large B-cell lymphoma with central nervous system involvement: A novel approach to diagnosis.

Abstract

The outcome of patients with diffuse large B-cell lymphoma (DLBCL) with central nervous system (CNS) recurrence is poor. However, there is currently no consensus regarding diagnostic techniques. The aim of the present study was to investigate the cerebrospinal fluid (CSF) protein profile of DLBCL and identify a potential novel method for the early diagnosis of patients with DLBCL at high risk for subsequent CNS involvement. The CSF proteomic profiling of patients with DLBCL and a control group were compared using label-free liquid chromatography-tandem mass spectrometry. Gene Ontology and pathway analyses were conducted using the Database for Annotation, Visualization and Integrated Discovery. The protein interactions were analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins database. In the present study, a total of 53 differentially expressed proteins with >1 log2 fold change (false discovery rate <0.01, P<0.05) were identified and quantified. These proteins appeared to be involved in platelet degranulation, innate immune response and cell adhesion. Two hub gene network modules were obtained by protein-protein interaction network analysis. Of these proteins, secreted protein acidic and rich in cysteine (SPARC) and proenkephalin (PENK) were significantly decreased in the CSF of patients with DLBCL, which appeared to be correlated with CNS involvement. The findings of the present study indicate that decreased expression levels of SPARC and PENK in the CSF may serve as early-phase biomarkers to evaluate the risk of CNS involvement in patients with DLBCL, enabling clinicians to offer prophylactic therapy at the time of diagnosis.