Author:
Hiratsuka Takuya,Ito Shinji,Sakai Rika,Yokose Tomoyuki,Endo Tatsuya,Daigo Yataro,Miyagi Yohei,Tsuruyama Tatsuaki
Abstract
Abstract
Background
The molecular pathology of diffuse large B cell lymphoma (DLBCL) has been extensively studied. Among DLBCL subtypes, the prognosis of CD5-positive DLBCL is worse than that of CD5-negative DLBCL, considering the central nervous system relapse and poor response to R-CHOP therapy. However, the molecular mechanisms underlying the tumorigenesis and progression of CD5-positive DLBCL remain unknown.
Methods
To identify molecular markers that can be targeted for treating DLBCL, a proteomic study was performed using liquid chromatography-mass spectrometry with chemically pretreated formalin-fixed paraffin-embedded specimens from CD5-positive (n = 5) and CD5-negative DLBCL patients (n = 6).
Results
Twenty-one proteins showed significant downregulation in CD5-positive DLBCL compared to CD5-negative DLBCL. Principal component analysis of protein expression profiling in CD5-positive and CD5-negative DLBCL revealed that DNAJB1, DDX3X, and BTK, which is one of the B cell phenotypic proteins, were the most significantly downregulated proteins and served as biomarkers that distinguished both groups. Additionally, a set of immunoglobulins, including IgG4, exhibited significant downregulation. Immunohistochemistry analysis for BTK demonstrated reduced staining in CD5-positive DLBCL compared to CD5-negative DLBCL.
Conclusions
In conclusion, DNAJB1 and DDX3X, BTK, and a set of immunoglobulins are promising biomarkers. Probably, the suppression of BCR signaling is the unique phenotype of CD5-positive DLBCL. This formalin-fixed paraffin-embedded (FFPE)-based profiling may help to develop novel therapeutic molecularly targeted drugs for treating DLBCL.
Funder
Ministry of Education, Culture, Sports, Science and Technology
Publisher
Springer Science and Business Media LLC
Subject
Clinical Biochemistry,Molecular Biology,Molecular Medicine,Clinical Biochemistry,Molecular Biology,Molecular Medicine
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