Proteome analysis of CD5-positive diffuse large B cell lymphoma FFPE tissue reveals downregulation of DDX3X, DNAJB1, and B cell receptor signaling pathway proteins including BTK and Immunoglobulins.

IF 2.8 3区医学 Q2 BIOCHEMICAL RESEARCH METHODS Clinical proteomics Pub Date : 2023-09-13 DOI:10.1186/s12014-023-09422-z

Takuya Hiratsuka, Shinji Ito, Rika Sakai, Tomoyuki Yokose, Tatsuya Endo, Yataro Daigo, Yohei Miyagi, Tatsuaki Tsuruyama

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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.

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cd5阳性弥漫性大B细胞淋巴瘤FFPE组织的蛋白质组学分析显示，DDX3X、DNAJB1和B细胞受体信号通路蛋白包括BTK和免疫球蛋白下调。

背景:弥漫性大B细胞淋巴瘤(DLBCL)的分子病理学已被广泛研究。在DLBCL亚型中，考虑到中枢神经系统复发和对R-CHOP治疗的反应较差，cd5阳性DLBCL的预后较cd5阴性DLBCL差。然而，cd5阳性DLBCL发生和发展的分子机制尚不清楚。方法:对cd5阳性(n = 5)和cd5阴性(n = 6) DLBCL患者进行化学预处理的福尔马林固定石蜡包埋标本，采用液相色谱-质谱法进行蛋白质组学研究，以鉴定可靶向治疗DLBCL的分子标记物。结果:与cd5阴性DLBCL相比，cd5阳性DLBCL中有21个蛋白表达显著下调。cd5阳性和cd5阴性DLBCL蛋白表达谱的主成分分析显示，DNAJB1、DDX3X和B细胞表型蛋白之一BTK是下调最显著的蛋白，可以作为区分两组的生物标志物。此外，一组免疫球蛋白，包括IgG4，表现出显著的下调。免疫组织化学分析显示，与cd5阴性DLBCL相比，cd5阳性DLBCL中BTK的染色减少。结论:DNAJB1和DDX3X、BTK和一组免疫球蛋白是有前景的生物标志物。可能，抑制BCR信号是cd5阳性DLBCL的独特表型。这种基于福尔马林固定石蜡包埋(FFPE)的分析可能有助于开发治疗DLBCL的新型治疗性分子靶向药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical proteomics BIOCHEMICAL RESEARCH METHODS-

CiteScore

5.80

自引率

2.60%

发文量

审稿时长

17 weeks

期刊介绍： Clinical Proteomics encompasses all aspects of translational proteomics. Special emphasis will be placed on the application of proteomic technology to all aspects of clinical research and molecular medicine. The journal is committed to rapid scientific review and timely publication of submitted manuscripts.